Therapy Of Thromboembolic Disease

The management of primary diseases resulting in the development of thromboembolism is discussed in related posts throughout this textbook. Therapy of thromboembolism should be directed toward the underlying disorder whenever possible. Therapeutic strategies for managing thromboembolism include short-term systemic anticoagulation and fibrinolysis followed by long-term antiplatelet or anticoagulant therapy to reduce the risk of rethrombosis.

Supportive Care

General patient care is critical for successful management of thrombosis. Analgesic agents should be considered for acute pain management. Fluid therapy should be administered when indicated to correct acid-base abnormalities and dehydration. Dextrose-containing fluids should be avoided whenever possible because they may cause endothelial damage, further promoting thrombosis. A risk of volume overload exists with heart failure or pulmonary hypertension and fluid therapy must be carefully monitored. Strict cage rest and oxygen therapy are indicated in cases of pulmonary thromboembolism or thrombosis associated with congestive heart failure (CHF).

Acute Anticoagulation

Heparin is the mainstay of acute anticoagulation. Anticoagulants prevent additional clots from forming but do not dissolve clots (see thrombolysis). Coumadin therapy for the long-term control of thrombosis is initiated after adequate hepariniza-tion has been achieved.

Heparin functions as a cofactor with antithrombin III, and together this complex exerts its effect by neutralizing factor X and thrombin. Heparin is inactivated by gastrointestinal (GI) enzymes when given orally and therefore must be administered by injection. Heparin is administered to prolong the baseline activated partial thromboplastin time (aPTT) to 1.5 to 3.0 times the baseline value. Prolongation of the aPTT or activated coagulation time (ACT) does not correlate well with heparin levels in cats and dogs, and measurement of plasma heparin levels may be more useful in monitoring heparin therapy. Although many different heparin doses have been advocated, little clinical data exist concerning efficacy. Doses of heparin required to achieve adequate heparin levels in cats with thromboembolism ranged from 175 U/kg every 6 hours to 475 U/kg every 8 hours, subcutaneously. In normal dogs the dose of heparin required to achieve adequate heparin concentrations was 250 U/kg every 6 hours, subcutaneously. The most common side effect of heparin therapy is hemorrhage. In the event of severe hemorrhage, heparin can be neutralized by protamine sulfate administration.

Low molecular weight (LMW) heparin is being increasingly used. Its anticoagulant effect is limited to blocking the activity of factor X. Because LMW heparin has a lower antithrombin effect than unfractionated heparin, LMW heparin does not markedly influence the PT or aPlT. Measurement of factor X activity has been used to assess the effect of LMW heparin. One advantage of LMW heparin is that it has a lower risk of hemorrhage than conventional hep-arin therapy. The optimal dose of LMW heparin in dogs and cats with thromboembolic disease remains to be determined.

Chronic Anticoagulation

Warfarin (Coumadin) is a vitamin K antagonist inhibiting the synthesis of vitamin K-dependent clotting proteins (prothrom-bin and factors VII, IX and X). In addition, warfarin reduces efficacy of the vitamin K-dependent regulatory proteins C and S. Proteins C and S are anticoagulant factors, and their function is the first to be inhibited by warfarin administration. Therefore heparin and warfarin administration are generally overlapped for 2 to 4 days to prevent a transient hypercoagulable state. Some animals appear to do well with just warfarin. Starting doses for warfarin are 0.25 to 0.5 mg every 24 hours in the cat and 0.1 to 0.2 mg/kg every 24 hours in the dog. Due to the high individual patient variability, close monitoring of PT is essential. Early recommendations were to maintain PT 1.5 times the baseline value, and more recent recommendations suggest attaining an international normalized ratio (INR) of 2:3. INR is calculated by the formula (patient PT/control PT). The ISI is a value specific to the tissue thromboplastin that is used in measuring the PT Coumadin is continued on a long-term basis to prevent recurrent TE. Studies documenting the optimal dose, efficacy, and duration of Coumadin therapy for specific thromboembolic diseases in dogs and cats are unknown.

The use of Coumadin is not without risks. The major risk is fatal hemorrhage, which occurs acutely and unexpectedly. Ideally, pets maintained on Coumadin should live indoors and be well supervised to prevent trauma and to monitor for hemorrhage. Periodic measurement of the PT should be done to ensure adequate dosing. Coumadin interacts with many drugs. The addition of medications to the treatment regimen of a pet on Coumadin should be done cautiously because certain drugs will raise the activity of Coumadin and predispose patients to bleeding. Some of these drugs are phenylbutazone, metronidazole, trimethoprim sulfa, and second- and third-generation cephalosporins. Barbiturates will decrease Coumadin anticoagulant effect. If bleeding complications occur, warfarin therapy is discontinued and administration of vitamin K is recommended.

Antiplatelet Therapy

Antiplatelet drugs have been advocated for long-term management to prevent rethrombosis. These drugs inhibit platelet aggregation and adhesion, preventing the formation of the hemostatic platelet plug. Aspirin inhibits cyclooxygenase, leading to decreased thromboxane A2 synthesis. This renders platelets nonfunctional by preventing their aggregation. Cats lack the enzyme needed to metabolize aspirin (glucuronyl transferase), making them sensitive to aspirin-induced platelet dysfunction. Doses of 0.5 mg/kg every 12 hours in the dog and 25 mg/kg twice weekly in the cat may decrease platelet aggregation. However, rethrombosis generally occurs despite aspirin therapy, although it is not known whether aspirin delays recrudescence. Additional antiplatelet drugs include dipyridamole and ticlopidine. Dipyridamole is thought to inhibit platelet aggregation by inhibition of platelet phospho-diesterase, leading to increased levels of cyclic adenosine monophosphate (cAMP) within platelets. Ticlopidine impairs fibrinogen binding and inhibits platelet aggregation induced by ADP and collagen. The use of these newer compounds has been limited thus far in veterinary medicine.


Thrombolytic agents such as streptokinase, urokinase, and tissue plasminogen activator (tPA) are potent activators of fib-rinolysis. These agents have been used with variable and often limited success in veterinary medicine.

Streptokinase binds plasminogen, and the complex transforms other plasminogen molecules into plasm in. Plasmin then binds to fibrin and causes thrombolysis. Streptokinase binds both free and clot-associated plasminogen. It also degrades factors V, VIII, and prothrombin, resulting in a massive systemic coagulation defect.

Streptokinase has been used to treat aortic thromboembolism (ATE) in cats with varying degrees of success. In one study of 46 cats, 15 were discharged from the hospital after streptokinase therapy with a median survival of 51 days. Reperfusion injury occurred in approximately 35% after thrombolysis, with streptokinase often resulting in fatal hyperkalemia and metabolic acidosis- Eleven of the cats developed clinical hemorrhage after streptokinase therapy. In three cats, hemorrhage was significant enough to require transfusion. Others reported conservative management (treatment of heart failure plus Coumadin or aspirin) of thromboembolism with a hospital discharge rate of 28%, which was similar to cats treated with streptokinase. One recommended dose of streptokinase for dogs and cats with thromboembolism is 90,000 U, intravenously administered over 20 to 30 minutes, followed by a maintenance infusion of 45,000 U for 7 to 12 hours. Infusions may be repeated over a total of 3 days.

Recombinant DNA technology produces t-PA, a serine protease. A complex forms between t-PA and fibrin, and that complex preferentially activates thrombus-associated plasminogen-resulting in rapid fibrinolysis. Life-threatening hemorrhage is the number one side effect. The half-life of t-PA in dogs is 2 to 3 minutes; consequendy, if bleeding occurs, stopping the infusion will result in the drug clearance from the system in 5 to 10 minutes. Because t-PA causes rapid thrombolysis, the risk of reperfusion syndrome and lethal hyperkalemia is substantial. In one report, 50% of cats with thromboembolism died acutely during t-PA therapy, with death attributed to hyperkalemia, severe anemia, and renal hemorrhage.


Amoxicillin (Amoxil, Amoxi-Tabs)


Highlights Of Prescribing Information

Bactericidal aminopenicillin with same spectrum as ampicillin (ineffective against bacteria that produce beta-lactamase)

Most likely adverse effects are GI-related, but hypersensitivity & other adverse effects rarely occur

Available in oral & parenteral dosage forms in USA

What Is Amoxicillin Used For?

The aminopenicillins have been used for a wide range of infections in various species. FDA-approved indications/species, as well as non-approved uses, are listed in the Dosages section below.

Pharmacology / Actions

Like other penicillins, amoxicillin is a time-dependent, bactericidal (usually) agent that acts by inhibiting cell wall synthesis. Although there may be some slight differences in activity against certain organisms, amoxicillin generally shares the same spectrum of activity and uses as ampicillin. Because it is better absorbed orally (in non-ruminants), higher serum levels maybe attained than with ampicillin.

Penicillins are usually bactericidal against susceptible bacteria and act by inhibiting mucopeptide synthesis in the cell wall resulting in a defective barrier and an osmotically unstable spheroplast. The exact mechanism for this effect has not been definitively determined, but beta-lactam antibiotics have been shown to bind to several enzymes (carboxypeptidases, transpeptidases, endopeptidases) within the bacterial cytoplasmic membrane that are involved with cell wall synthesis. The different affinities that various beta-lactam antibiotics have for these enzymes (also known as penicillin-binding proteins; PBPs) help explain the differences in spectrums of activity the drugs have that are not explained by the influence of beta-lactamases. Like other beta-lactam antibiotics, penicillins are generally considered more effective against actively growing bacteria.

The aminopenicillins, also called the “broad-spectrum” or ampicillin penicillins, have increased activity against many strains of gram-negative aerobes not covered by either the natural penicillins or penicillinase-resistant penicillins, including some strains of E. coli, Klebsiella, and Haemophilus. Like the natural penicillins, they are susceptible to inactivation by beta-lactamase-producing bacteria (e.g., Staph aureus). Although not as active as the natural penicillins, they do have activity against many anaerobic bacteria, including Clostridial organisms. Organisms that are generally not susceptible include Pseudomonas aeruginosa, Serratia, Indole-positive Proteus {Proteus mirahilis is susceptible), Enterobacter, Citrobacter, and Acinetobacter. The aminopenicillins also are inactive against Rickettsia, mycobacteria, fungi, Mycoplasma, and viruses.

In order to reduce the inactivation of penicillins by beta-lactamases, potassium clavulanate and sulbactam have been developed to inactivate these enzymes and thus extend the spectrum of those penicillins. When used with a penicillin, these combinations are often effective against many beta-lactamase-producing strains of otherwise resistant E. coli, Pasturella spp., Staphylococcus spp., Klebsiella, and Proteus. Type I beta-lactamases that are often associated with E. coli, Enterobacter, and Pseudomonas are not generally inhibited by clavulanic acid.


Amoxicillin trihydrate is relatively stable in the presence of gastric acid. After oral administration, it is about 74-92% absorbed in humans and monogastric animals. Food will decrease the rate, but not the extent of oral absorption and many clinicians suggest giving the drug with food, particularly if there is concomitant associated GI distress. Amoxicillin serum levels will generally be 1.5-3 times greater than those of ampicillin after equivalent oral doses.

After absorption, the volume of distribution for amoxicillin is approximately 0.3 L/kg in humans and 0.2 L/kg in dogs. The drug is widely distributed to many tissues, including liver, lungs, prostate (human), muscle, bile, and ascitic, pleural and synovial fluids. Amoxicillin will cross into the CSF when meninges are inflamed in concentrations that may range from 10-60% of those found in serum. Very low levels of the drug are found in the aqueous humor, and low levels found in tears, sweat and saliva. Amoxicillin crosses the placenta, but it is thought to be relatively safe to use during pregnancy. It is approximately 17-20% bound to human plasma proteins, primarily albumin. Protein binding in dogs is approximately 13%. Milk levels of amoxicillin are considered low.

Amoxicillin is eliminated primarily through renal mechanisms, principally by tubular secretion, but some of the drug is metabolized by hydrolysis to penicilloic acids (inactive) and then excreted in the urine. Elimination half-lives of amoxicillin have been reported as 45-90 minutes in dogs and cats, and 90 minutes in cattle. Clearance is reportedly 1.9 mL/kg/min in dogs.

Before you take Amoxicillin

Contraindications / Precautions / Warnings

Penicillins are contraindicated in patients with a history of hyper-sensitivity to them. Because there may be cross-reactivity, use penicillins cautiously in patients who are documented hypersensitive to other beta-lactam antibiotics (e.g., cephalosporins, cefamycins, carbapenems).

Do not administer penicillins, cephalosporins, or macrolides to rabbits, guinea pigs, chinchillas, hamsters, etc. or serious enteritis and clostridial enterotoxemia may occur.

Do not administer systemic antibiotics orally in patients with septicemia, shock, or other grave illnesses as absorption of the medication from the GI tract may be significantly delayed or diminished. Parenteral (preferably IV) routes should be used for these cases.

Adverse Effects

Adverse effects with the penicillins are usually not serious and have a relatively low frequency of occurrence.

Hypersensitivity reactions unrelated to dose can occur with these agents and can manifest as rashes, fever, eosinophilia, neutropenia, agranulocytosis, thrombocytopenia, leukopenia, anemias, lymphadenopathy, or full-blown anaphylaxis.

When given orally, penicillins may cause GI effects (anorexia, vomiting, diarrhea). Because the penicillins may alter gut flora, antibiotic-associated diarrhea can occur and allow the proliferation of resistant bacteria in the colon (superinfections).

High doses or very prolonged use have been associated with neurotoxicity (e.g., ataxia in dogs). Although the penicillins are not considered hepatotoxic, elevated liver enzymes have been reported. Other effects reported in dogs include tachypnea, dyspnea, edema and tachycardia.

Reproductive / Nursing Safety

Penicillins have been shown to cross the placenta; safe use during pregnancy has not been firmly established, but neither have there been any documented teratogenic problems associated with these drugs. However, use only when the potential benefits outweigh the risks. In humans, the FDA categorizes this drug as category B for use during pregnancy () In a separate system evaluating the safety of drugs in canine and feline pregnancy (), this drug is categorized as in class: A (Probably safe. Although specific studies may not have proved the safety of all drugs in dogs and cats, there are no reports of adverse effects in laboratory animals or women.)

Overdosage / Acute Toxicity

Acute oral penicillin overdoses are unlikely to cause significant problems other than GI distress but other effects are possible (see Adverse Effects). In humans, very high dosages of parenteral penicillins, especially in patients with renal disease, have induced CNS effects.

How to use Amoxicillin

Amoxicillin dosage for dogs:

For susceptible infections:

a) For Gram-positive infections: 10 mg/kg PO, IM, SC twice daily for at least 2 days after symptoms subside.

For Gram-negative infections: 20 mg/kg PO three times daily or IM, SC twice daily for at least 2 days after symptoms subside ()

b) For susceptible UTI’s: 10-20 mg/kg PO q12h for 5-7 days. For susceptible systemic infections (bacteremia/sepsis): 22-30 mg/kg IV, IM, SC q8h for 7 days.

For susceptible orthopedic infections: 22-30 mg/kg IV, IM, SC, or PO q6-8h for 7-10 days. ()

c) For Lyme disease: 22 mg/kg PO q12h for 21-28 days ()

Amoxicillin dosage for cats:

For susceptible infections:

a) For Gram-positive infections: 10 mg/kg PO, IM, SC twice daily for at least 2 days after symptoms subside.

For Gram-negative infections: 20 mg/kg PO three times daily or IM, SC twice daily for at least 2 days after symptoms subside ()

b) For susceptible UTI’s and soft tissue infections: 50 mg (total dose per cat) or 11-22 mg/kg PO once daily for 5-7 days. For sepsis: 10-20 mg/kg IV, SC, or PO q12h for as long as necessary. Note: Duration of treatment are general guidelines, generally treat for at least 2 days after all signs of infection are gone. ()

c) C. perfringens, bacterial overgrowth (GI): 22 mg/kg PO once daily for 5 days ()

d) C. perfringens enterotoxicosis: 11-22 mg/kg PO two to three times daily for 7 days ()

e) For treating H. pylori infections using triple therapy: amoxi-cillin 20 mg/kg PO twice daily for 14 days; metronidazole 10-15 mg/kg PO twice daily; clarithromycin 7.5 mg/kg PO twice daily ()

Amoxicillin dosage for ferrets:

For eliminating Helicobacter gastritis infections:

a) Using triple therapy: Metronidazole 22 mg/kg, amoxicillin 22 mg/kg and bismuth subsalicylate (original Pepto-Bismol) 17.6 mg/kg PO. Give each 3 times daily for 3-4 weeks. ()

b) Using triple therapy: Metronidazole 20 mg/kg PO q12h, amoxicillin 20 mg/kg PO q12h and bismuth subsalicylate 17.5 mg/kg PO q8h. Give 21 days. Sucralfate (25 mg/kg PO q8h) and famotidine (0.5 mg/kg PO once daily) are also used. Fluids and assisted feeding should be continued while the primary cause of disease is investigated. ()

For susceptible infections:

a) 10-35 mg/kg PO or SC twice daily ()

Amoxicillin dosage for rabbits, rodents, and small mammals:

Note: See warning above in Contraindications a) Hedgehogs: 15 mg/kg IM or PO q12h ()

Amoxicillin dosage for cattle:

For susceptible infections:

a) 6-10 mg/kg SC or IM q24h (Withdrawal time = 30 days) ()

b) For respiratory infections: 11 mg/kg IM or SC q12h ()

c) Calves: Amoxicillin trihydrate: 7 mg/kg PO q8-12h ()

Amoxicillin dosage for horses:

For susceptible infections:

a) For respiratory infections: 20-30 mg/kg PO q6h ()

b) Foals: Amoxicillin Sodium: 15-30 mg/kg IV or IM q6-8h; amoxicillin trihydrate suspension: 25-40 mg/kg PO q8h; amoxicillin/clavulanate 15-25 mg/kg IV q6-8h ()

Amoxicillin dosage for birds:

For susceptible infections:

a) For most species: 150-175 mg/kg PO once to twice daily (using 50 mg/mL suspension) ()

b) 100 mg/kg q8h PO ()

c) 100 mg/kg q8h, IM, SC, PO ()

d) Ratites: 15-22 mg/kg PO twice daily; in drinking water: 250 mg/gallon for 3-5 days ()

Amoxicillin dosage for reptiles:

For susceptible infections:

a) For all species: 22 mg/kg PO ql2 -24h; not very useful unless used in combination with aminoglycosides ()

Client Information

■ The oral suspension should preferably be refrigerated, but refrigeration is not absolutely necessary; any unused oral suspension should be discarded after 14 days

■ Amoxicillin may be administered orally without regard to feeding status

■ If the animal develops gastrointestinal symptoms (e.g., vomiting, anorexia), giving with food may be of benefit

Chemistry / Synonyms

An aminopenicillin, amoxicillin is commercially available as the trihydrate. It occurs as a practically odorless, white, crystalline powder that is sparingly soluble in water. Amoxicillin differs structurally from ampicillin only by having an additional hydroxyl group on the phenyl ring.

Amoxicillin may also be known as: amoxycillin, p-hydroxyampicillin, or BRL 2333; many trade names are available.

Storage / Stability / Compatibility

Amoxicillin capsules, tablets, and powder for oral suspension should be stored at room temperature (15-30°C) in tight containers. After reconstitution, the oral suspension should preferably be refrigerated (refrigeration not absolutely necessary) and any unused product discarded after 14 days.

Dosage Forms / Regulatory Status/Withdrawal Times

Veterinary-Labeled Products:

Amoxicillin Oral Tablets: 50 mg, 100 mg, 150 mg, 200 mg, & 400 mg; Amoxi-Tabs (Pfizer); (Rx). Approved for use in dogs and cats.

Amoxicillin Powder for Oral Suspension 50 mg/mL (after reconstitution) in 15 mL or 30 mL bottles; Amoxi-Drop (Pfizer); (Rx). Approved for use in dogs and cats.

Amoxicillin Intramammary Infusion 62.5 mg/syringe in 10 mL syringes; Amoxi-Mast (Schering-Plough); (Rx). Approved for use in lactating dairy cattle. Slaughter withdrawal (when administered as labeled) = 12 days; Milk withdrawal (when administered as labeled) = 60 hours.

Human-Labeled Products:

Amoxicillin Tablets (chewable) (as trihydrate): 125 mg, 200 mg, 250 mg, & 400 mg; Amoxf/(GlaxoSmithKline); generic; (Rx)

Amoxicillin Tablets (as trihydrate): 500 mg & 875 mg; Amoxil (GlaxoSmithKline); generic; (Rx)

Amoxicillin Capsules (as trihydrate): 250 mg, & 500 mg; Amoxil (GlaxoSmithKline); generic; (Rx)

Amoxicillin (as trihydrate) Powder for Oral Suspension: 50 mg/mL (in 15 and 30 mL bottles), 125 mg/5 mL in 80 mL & 150 mL; 200 mg/5 mL in 50 mL, 75 mL & 100 mL; 250 mg/5 mL in 80 mL, 100 mL & 150 mL; 400 mg/5 mL in 50 mL, 75 mL & 100 mL; Amoxil & Amoxil Pediatric Drops (GlaxoSmithKline); (Apothecon), Trimox (Sandoz); generic; (Rx)

AmoxiciUin Tablets for Oral Suspension: 200 mg & 400 mg; Disper-Mox (Ranbaxy); (Rx)


Aminophylline Theophylline

Phosphodiesterase Inhibitor Bronchodilator

Highlights Of Prescribing Information

Bronchodilator drug with diuretic activity; used for bronchospasm & cardiogenic pulmonary edema

Narrow therapeutic index in humans, but dogs appear to be less susceptible to toxic effects at higher plasma levels

Therapeutic drug monitoring recommended

Many drug interactions

What Is Aminophylline Theophylline Used For?

The theophyllines are used primarily for their broncho dilatory effects, often in patients with myocardial failure and/or pulmonary edema. While they are still routinely used, the methylxanthines must be used cautiously due to their adverse effects and toxicity.


The theophyllines competitively inhibit phosphodiesterase thereby increasing amounts of cyclic AMP which then increase the release of endogenous epinephrine. The elevated levels of cAMP may also inhibit the release of histamine and slow reacting substance of anaphylaxis (SRS-A). The myocardial and neuromuscular transmission effects that the theophyllines possess maybe a result of translocating intracellular ionized calcium.

The theophyllines directly relax smooth muscles in the bronchi and pulmonary vasculature, induce diuresis, increase gastric acid secretion and inhibit uterine contractions. They have weak chronotropic and inotropic action, stimulate the CNS and can cause respiratory stimulation (centrally-mediated).


The pharmacokinetics of theophylline have been studied in several domestic species. After oral administration, the rate of absorption of the theophyllines is limited primarily by the dissolution of the dosage form in the gut. In studies in cats, dogs, and horses, bioavail-abilities after oral administration are nearly 100% when non-sustained release products are used. One study in dogs that compared various sustained-release products (), found bioavailabilities ranging from approximately 30-76% depending on the product used.

Theophylline is distributed throughout the extracellular fluids and body tissues. It crosses the placenta and is distributed into milk (70% of serum levels). In dogs, at therapeutic serum levels only about 7-14% is bound to plasma proteins. The volume of distribution of theophylline for dogs has been reported to be 0.82 L/kg. The volume of distribution in cats is reported to be 0.46 L/kg, and in horses, 0.85-1.02 L/kg. Because of the low volumes of distribution and theophylline’s low lipid solubility, obese patients should be dosed on a lean body weight basis.

Theophylline is metabolized primarily in the liver (in humans) to 3-methylxanthine which has weakbronchodilitory activity. Renal clearance contributes only about 10% to the overall plasma clearance of theophylline. The reported elimination half-lives (mean values) in various species are: dogs = 5.7 hours; cats = 7.8 hours, pigs = 11 hours; and horses = 11.9 to 17 hours. In humans, there are very wide interpatient variations in serum half-lives and resultant serum levels. It could be expected that similar variability exists in veterinary patients, particularly those with concurrent illnesses.

Before you take Aminophylline Theophylline

Contraindications / Precautions / Warnings

The theophyllines are contraindicated in patients who are hypersensitive to any of the xanthines, including theobromine or caffeine. Patients who are hypersensitive to ethylenediamine should not take aminophylline.

The theophyllines should be administered with caution in patients with severe cardiac disease, seizure disorders, gastric ulcers, hyperthyroidism, renal or hepatic disease, severe hypoxia, or severe hypertension. Because it may cause or worsen preexisting arrhythmias, patients with cardiac arrhythmias should receive theophylline only with caution and enhanced monitoring. Neonatal and geriatric patients may have decreased clearances of theophylline and be more sensitive to its toxic effects. Patients with CHF may have prolonged serum half-lives of theophylline.

Adverse Effects

The theophyllines can produce CNS stimulation and gastrointestinal irritation after administration by any route. Most adverse effects are related to the serum level of the drug and may be symptomatic of toxic blood levels; dogs appear to tolerate levels that may be very toxic to humans. Some mild CNS excitement and GI disturbances are not uncommon when starting therapy and generally resolve with chronic administration in conjunction with monitoring and dosage adjustments.

Dogs and cats can exhibit clinical signs of nausea and vomiting, insomnia, increased gastric acid secretion, diarrhea, polyphagia, polydipsia, and polyuria. Side effects in horses are generally dose related and may include: nervousness, excitability (auditory, tactile, and visual), tremors, diaphoresis, tachycardia, and ataxia. Seizures or cardiac dysrhythmias may occur in severe intoxications.

Reproductive / Nursing Safety

In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.)

Overdosage / Acute Toxicity

Clinical signs of toxicity (see above) are usually associated with levels greater than 20 mcg/mL in humans and become more severe as the serum level exceeds that value. Tachycardias, arrhythmias, and CNS effects (seizures, hyperthermia) are considered the most life-threatening aspects of toxicity. Dogs appear to tolerate serum levels higher than 20 mcg/mL.

Treatment of theophylline toxicity is supportive. After an oral ingestion, the gut should be emptied, charcoal and a cathartic administered using the standardized methods and cautions associated with these practices. Patients suffering from seizures should have an adequate airway maintained and treated with IV diazepam. The patient should be constantly monitored for cardiac arrhythmias and tachycardia. Fluid and electrolytes should be monitored and corrected as necessary. Hyperthermia may be treated with phenothiazines and tachycardia treated with propranolol if either condition is considered life threatening.

How to use Aminophylline Theophylline

Note: Theophyllines have a low therapeutic index; determine dosage carefully. Because of aminophylline/theophylline’s pharmacokinet-ic characteristics, it should be dosed on a lean body weight basis in obese patients. Dosage conversions between aminophylline and theophylline can be easily performed using the information found in the Chemistry section below. Aminophylline causes intense local pain when administered IM and is rarely used or recommended via this route.

Aminophylline Theophylline dosage for dogs:

a) Using Theochron Extended-Release Tablets or Theo-Cap Extended-Release Capsules: Give 10 mg/kg PO every 12 hours initially, if no adverse effects are observed and the desired clinical effect is not achieved, give 15 mg/kg PO q12h while monitoring for adverse effects. ()

b) For adjunctive medical therapy for mild clinical signs associated with tracheal collapse (<50% collapse): aminophylline: 11 mg/kg PO, IM or IV three times daily. ()

c) For adjunctive therapy of severe, acute pulmonary edema and bronchoconstriction: Aminophylline 4-8 mg/kg IV or IM, or 6-10 mg/kg PO every 8 hours. Long-term use is not recommended. ()

d) For cough: Aminophylline: 10 mg/kg PO, IV three times daily ()

e) As a broncho dilator tor collapsing trachea: 11 mg/kg PO or IV q6- 12h ()

Aminophylline Theophylline dosage for cats:

a) Using Theo-Dur 20 mg/kg PO once daily in the PM; using Slo-Bid 25 mg/kg PO once daily in the PM (Johnson 2000) [Note: The products Theo-Dur and Slo-Bid mentioned in this reference are no longer available in the USA. Although hard data is not presently available to support their use in cats, a reasonable alternative would be to cautiously use the dog dose and products mentioned above in the reference by Bach et al — Plumb]

b) Using aminophylline tablets: 6.6. mg/kg PO twice daily; using sustained release tablets (Theo-Dur): 25-50 mg (total dose) per cat PO in the evening ()

c) For adjunctive medical therapy for mild clinical signs associated with tracheal collapse (<50% collapse): aminophylline: 5 mg/kg PO, two times daily. ()

d) For adjunctive therapy for bronchoconstriction associated with fulminant CHF: Aminophylline 4-8 mg/kg SC, IM, IV q8-12h. ()

e) For cough: Aminophylline: 5 mg/kg PO twice daily ()

Aminophylline Theophylline dosage for ferrets:

a) 4.25 mg/kg PO 2-3 times a day ()

Aminophylline Theophylline dosage for horses:

(Note: ARCI UCGFS Class 3 Aminophylline Theophylline)

NOTE: Intravenous aminophylline should be diluted in at least 100 mL of D5W or normal saline and administered slowly (not >25 mg/min). For adjunctive treatment of pulmonary edema:

a) Aminophylline 2-7 mg/kg IV q6- 12h; Theophylline 5-15 mg/kg PO q12h ()

b) 11 mg/kg PO or IV q8-12h. To “load” may either double the initial dose or give both the oral and IV dose at the same time. IV infusion should be in approximately 1 liter of IV fluids and given over 20-60 minutes. Recommend monitoring serum levels. ()

For adjunctive treatment for heaves (RAO):

a) Aminophylline: 5-10 mg/kg PO or IV twice daily. ()

b) Aminophylline: 4-6 mg/kg PO three times a day. ()


■ Therapeutic efficacy and clinical signs of toxicity

■ Serum levels at steady state. The therapeutic serum levels of theophylline in humans are generally described to be between 10-20 micrograms/mL. In small animals, one recommendation for monitoring serum levels is to measure trough concentration; level should be at least above 8-10 mcg/mL (Note: Some recommend not exceeding 15 micrograms/mL in horses).

Client Information

■ Give dosage as prescribed by veterinarian to maximize the drug’s benefit

Chemistry / Synonyms

Xanthine derivatives, aminophylline and theophylline are considered to be respiratory smooth muscle relaxants but, they also have other pharmacologic actions. Aminophylline differs from theophylline only by the addition of ethylenediamine to its structure and may have different amounts of molecules of water of hydration. 100 mg of aminophylline (hydrous) contains approximately 79 mg of theophylline (anhydrous); 100 mg of aminophylline (anhydrous) contains approximately 86 mg theophylline (anhydrous). Conversely, 100 mg of theophylline (anhydrous) is equivalent to 116 mg of aminophylline (anhydrous) and 127 mg aminophylline (hydrous).

Aminophylline occurs as bitter-tasting, white or slightly yellow granules or powder with a slight ammoniacal odor and a pKa of 5. Aminophylline is soluble in water and insoluble in alcohol.

Theophylline occurs as bitter-tasting, odorless, white, crystalline powder with a melting point between 270-274°C. It is sparingly soluble in alcohol and only slightly soluble in water at a pH of 7, but solubility increases with increasing pH.

Aminophylline may also be known as: aminofilina, aminophyllinum, euphyllinum, metaphyllin, theophyllaminum, theophylline and ethylenediamine, theophylline ethylenediamine compound, or theophyllinum ethylenediaminum; many trade names are available.

Theophylline may also be known as: anhydrous theophylline, teofillina, or theophyllinum; many trade names are available.

Storage / Stability/Compatibility

Unless otherwise specified by the manufacturer, store aminophylline and theophylline oral products in tight, light-resistant containers at room temperature. Do not crush or split sustained-release oral products unless label states it is permissible.

Aminophylline for injection should be stored in single-use containers in which carbon dioxide has been removed. It should also be stored at temperatures below 30°C and protected from freezing and light. Upon exposure to air (carbon dioxide), aminophylline will absorb carbon dioxide, lose ethylenediamine and liberate free theophylline that can precipitate out of solution. Do not inject aminophylline solutions that contain either a precipitate or visible crystals.

Aminophylline for injection is reportedly compatible when mixed with all commonly used IV solutions, but may be incompatible with 10% fructose or invert sugar solutions.

Aminophylline is reportedly compatible when mixed with the following drugs: amobarbital sodium, bretylium tosylate, calcium gluconate, chloramphenicol sodium succinate, dexamethasone sodium phosphate, dopamine HCL, erythromycin lactobionate, heparin sodium, hydro cortisone sodium succinate, lidocaine HCL, mephentermine sulfate, methicillin sodium, methyldopate HCL, metronidazole with sodium bicarbonate, pentobarbital sodium, phenobarbital sodium, potassium chloride, secobarbital sodium, sodium bicarbonate, sodium iodide, terbutaline sulfate, thiopental sodium, and verapamil HCL

Aminophylline is reportedly incompatible (or data conflicts) with the following drugs: amikacin sulfate, ascorbic acid injection, bleomycin sulfate, cephalothin sodium, cephapirin sodium, clindamycin phosphate, codeine phosphate, corticotropin, dimenhydrinate, dobutamine HCL, doxorubicin HCL, epinephrine HCL, erythromycin gluceptate, hydralazine HCL, hydroxyzine HCL, insulin (regular), isoproterenol HCL, levorphanol bitartrate, meperidine HCL, methadone HCL, methylprednisolone sodium succinate, morphine sulfate, nafcillin sodium, norepinephrine bitartrate, oxytetracycline, penicillin G potassium, pentazocine lactate, procaine HCL, prochlorperazine edisylate or mesylate, promazine HCL, promethazine HCL, sulfisoxazole diolamine, tetracycline HCL, vancomycin HCL, and vitamin B complex with C. Compatibility is dependent upon factors such as pH, concentration, temperature, and diluent used and it is suggested to consult specialized references for more specific information.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products: None

The ARCI (Racing Commissioners International) has designated this drug as a class 3 substance. See the appendix for more information.

Human-Labeled Products:

The listing below is a sampling of products and sizes available; consult specialized references for a more complete listing.

Aminophylline Tablets: 100 mg (79 mg theophylline) & 200 mg (158 mg theophylline); generic; (Rx)

Aminophylline Injection: 250 mg (equiv. to 197 mg theophylline) mL in 10 mL & 20 mL vials, amps and syringes; generic; (Rx)

Theophylline Time Released Capsules and Tablets: 100 mg, 125 mg 200 mg, 300 mg, 400 mg, 450 mg, & 600 mg. (Note: Different products have different claimed release rates which may or may not correspond to actual times in veterinary patients; Theophylline Extended-Release (Dey); Theo-24 (UCB Pharma); Theophylline SR (various); Theochron (Forest, various); Theophylline (Able); Theocron (Inwood); Uniphyl (Purdue Frederick); generic; (Rx)

Theophylline Tablets and Capsules: 100 mg, 200 mg, & 300 mg; Bronkodyl (Winthrop); Elixophyllin (Forest); generic; (Rx)

Theophylline Elixir: 80 mg/15 mL (26.7 mg/5 mL) in pt, gal, UD 15 and 30 mL, Asmalix (Century); Elixophyllin (Forest); Lanophyllin (Lannett); generic; (Rx)

Theophylline & Dextrose Injection: 200 mg/container in 50 mL (4 mg/mL) & 100 mL (2 mg/mL); 400 mg/container in 100 mL (4 mg/ mL), 250 mL (1.6 mg/mL), 500 mL (0.8 mg/mL) & 1000 mL (0.4 mg/mL); 800 mg/container in 250 mL (3.2 mg/mL), 500 mL (1.6 mg/mL) & 1000 mL (0.8 mg/mL); Theophylline & 5% Dextrose (Abbott & Baxter); (Rx)


Amikacin Sulfate (Amikin, Amiglyde-V)

Aminoglycoside Antibiotic

Highlights Of Prescribing Information

Parenteral aminoglycoside antibiotic that has good activity against a variety of bacteria, predominantly gram-negative aerobic bacilli

Adverse Effects: Nephrotoxicity, ototoxicity, neuromuscu-lar blockade

Cats may be more sensitive to toxic effects

Risk factors for toxicity: Preexisting renal disease, age (both neonatal & geriatric), fever, sepsis & dehydration

Now usually dosed once daily when used systemically

What Is Amikacin Sulfate Used For?

While parenteral use is only approved in dogs, amikacin is used clinically to treat serious gram-negative infections in most species. It is often used in settings where gentamicin-resistant bacteria are a clinical problem. The inherent toxicity of the aminoglycosides limit their systemic use to serious infections when there is either a documented lack of susceptibility to other, less toxic antibiotics or when the clinical situation dictates immediate treatment of a presumed gram-negative infection before culture and susceptibility results are reported.

Amikacin is also approved for intrauterine infusion in mares. It is used with intra-articular injection in foals to treat gram-negative septic arthritis.


Amikacin, like the other aminoglycoside antibiotics, act on susceptible bacteria presumably by irreversibly binding to the 30S ribosomal subunit thereby inhibiting protein synthesis. It is considered a bactericidal concentration-dependent antibiotic.

Amikacin’s spectrum of activity includes: coverage against many aerobic gram-negative and some aerobic gram-positive bacteria, including most species of E. coli, Klebsiella, Proteus, Pseudomonas, Salmonella, Enterobacter, Serratia, and Shigella, Mycoplasma, and Staphylococcus. Several strains of Pseudomonas aeruginosa, Proteus, and Serratia that are resistant to gentamicin will still be killed by amikacin.

Antimicrobial activity of the aminoglycosides is enhanced in an alkaline environment.

The aminoglycoside antibiotics are inactive against fungi, viruses and most anaerobic bacteria.


Amikacin, like the other aminoglycosides is not appreciably absorbed after oral or intrauterine administration, but is absorbed from topical administration (not from skin or the urinary bladder) when used in irrigations during surgical procedures. Patients receiving oral aminoglycosides with hemorrhagic or necrotic enteritises may absorb appreciable quantities of the drug. After IM administration to dogs and cats, peak levels occur from ½1 hour later. Subcutaneous injection results in slightly delayed peak levels and with more variability than after IM injection. Bio availability from extravascular injection (IM or SC) is greater than 90%.

After absorption, aminoglycosides are distributed primarily in the extracellular fluid. They are found in ascitic, pleural, pericardial, peritoneal, synovial and abscess fluids; high levels are found in sputum, bronchial secretions and bile. Aminoglycosides are minimally protein bound (<20%, streptomycin 35%) to plasma proteins. Aminoglycosides do not readily cross the blood-brain barrier nor penetrate ocular tissue. CSF levels are unpredictable and range from 0-50% of those found in the serum. Therapeutic levels are found in bone, heart, gallbladder and lung tissues after parenteral dosing. Aminoglycosides tend to accumulate in certain tissues such as the inner ear and kidneys, which may help explain their toxicity. Volumes of distribution have been reported to be 0.15-0.3 L/kg in adult cats and dogs, and 0.26-0.58 L/kg in horses. Volumes of distribution may be significantly larger in neonates and juvenile animals due to their higher extracellular fluid fractions. Aminoglycosides cross the placenta; fetal concentrations range from 15-50% of those found in maternal serum.

Elimination of aminoglycosides after parenteral administration occurs almost entirely by glomerular filtration. The approximate elimination half-lives for amikacin have been reported to be 5 hours in foals, 1.14-2.3 hours in adult horses, 2.2-2.7 hours in calves, 1-3 hours in cows, 1.5 hours in sheep, and 0.5-2 hours in dogs and cats. Patients with decreased renal function can have significantly prolonged half-lives. In humans with normal renal function, elimination rates can be highly variable with the aminoglycoside antibiotics.

Before you take Amikacin Sulfate

Contraindications / Precautions / Warnings

Aminoglycosides are contraindicated in patients who are hypersensitive to them. Because these drugs are often the only effective agents in severe gram-negative infections, there are no other absolute contraindications to their use. However, they should be used with extreme caution in patients with preexisting renal disease with concomitant monitoring and dosage interval adjustments made. Other risk factors for the development of toxicity include age (both neonatal and geriatric patients), fever, sepsis and dehydration.

Because aminoglycosides can cause irreversible ototoxicity, they should be used with caution in “working” dogs (e.g., “seeing-eye,” herding, dogs for the hearing impaired, etc.).

Aminoglycosides should be used with caution in patients with neuromuscular disorders (e.g., myasthenia gravis) due to their neuromuscular blocking activity.

Because aminoglycosides are eliminated primarily through renal mechanisms, they should be used cautiously, preferably with serum monitoring and dosage adjustment in neonatal or geriatric animals.

Aminoglycosides are generally considered contraindicated in rabbits/hares as they adversely affect the GI flora balance in these animals.

Adverse Effects

The aminoglycosides are infamous for their nephrotoxic and ototox-ic effects. The nephrotoxic (tubular necrosis) mechanisms of these drugs are not completely understood, but are probably related to interference with phospholipid metabolism in the lysosomes of proximal renal tubular cells, resulting in leakage of proteolytic enzymes into the cytoplasm. Nephrotoxicity is usually manifested by: increases in BUN, creatinine, nonprotein nitrogen in the serum, and decreases in urine specific gravity and creatinine clearance. Proteinuria and cells or casts may be seen in the urine. Nephrotoxicity is usually reversible once the drug is discontinued. While gentamicin may be more nephrotoxic than the other aminoglycosides, the incidences of nephrotoxicity with all of these agents require equal caution and monitoring.

Ototoxicity (8th cranial nerve toxicity) of the aminoglycosides can manifest by either auditory and/or vestibular clinical signs and may be irreversible. Vestibular clinical signs are more frequent with streptomycin, gentamicin, or tobramycin. Auditory clinical signs are more frequent with amikacin, neomycin, or kanamycin, but either form can occur with any of these drugs. Cats are apparently very sensitive to the vestibular effects of the aminoglycosides.

The aminoglycosides can also cause neuromuscular blockade, facial edema, pain/inflammation at injection site, peripheral neuropathy and hypersensitivity reactions. Rarely, GI clinical signs, hematologic and hepatic effects have been reported.

Reproductive / Nursing Safety

Aminoglycosides can cross the placenta and while rare, may cause 8th cranial nerve toxicity or nephrotoxicity in fetuses. Because the drug should only be used in serious infections, the benefits of therapy may exceed the potential risks. In humans, the FDA categorizes this drug as category C for use during pregnancy (Animal studies have shown an adverse effect on the fetus, hut there are no adequate studies in humans; or there are no animal reproduction studies and no adequate studies in humans.) In a separate system evaluating the safety of drugs in canine and feline pregnancy (), this drug is categorized as in class: C (These drugs may have potential risks. Studies in people or laboratory animals have uncovered risks, and these drugs should he used cautiously as a last resort when the benefit of therapy clearly outweighs the risks.)

Aminoglycosides are excreted in milk. While potentially, amikacin ingested with milk could alter GI flora and cause diarrhea, amikacin in milk is unlikely to be of significant concern after the first few days of life (colostrum period).

Overdosage / Acute Toxicity

Should an inadvertent overdosage be administered, three treatments have been recommended. Hemodialysis is very effective in reducing serum levels of the drug but is not a viable option for most veterinary patients. Peritoneal dialysis also will reduce serum levels but is much less efficacious. Complexation of drug with either carbenicillin or ticarcillin (12-20 g/day in humans) is reportedly nearly as effective as hemodialysis. Since amikacin is less affected by this effect than either tobramycin or gentamicin, it is assumed that reduction in serum levels will also be minimized using this procedure.

How to use Amikacin Sulfate

Note: Most infectious disease clinicians now agree that aminoglycosides should be dosed once a day in most patients (mammals). This dosing regimen yields higher peak levels with resultant greater bacterial kill, and as aminoglycosides exhibit a “post-antibiotic effect”, surviving susceptible bacteria generally do not replicate as rapidly even when antibiotic concentrations are below MIC. Periods where levels are low may also decrease the “adaptive resistance” (bacteria take up less drug in the presence of continuous exposure) that can occur. Once daily dosing may decrease the toxicity of aminoglycosides as lower urinary concentrations may mean less uptake into renal tubular cells. However, patients who are neutropenic (or otherwise immunosuppressed) may benefit from more frequent dosing (q8h). Patients with significantly diminished renal function who must receive aminoglycosides may need to be dosed at longer intervals than once daily. Clinical drug monitoring is strongly suggested for these patients.

Amikacin Sulfate dosage for dogs:

For susceptible infections:

a) Sepsis: 20 mg/kg once daily IV ()

b) 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). ()

c) 15-30 mg/kg IV, IM or SC once daily (q24h) ()

Amikacin Sulfate dosage for cats:

For susceptible infections:

a) Sepsis: 20 mg/kg once daily IV ()

b) 15 mg/kg (route not specified) once daily (q24h). Neutropenic or immunocompromised patients may still need to be dosed q8h (dose divided). ()

c) 10-15 mg/kg IV, IM or SC once daily (q24h) ()

Amikacin Sulfate dosage for ferrets:

For susceptible infections:

a) 8-16 mg/kg IM or IV once daily ()

b) 8-16 mg/kg/day SC, IM, IV divided q8-24h ()

Amikacin Sulfate dosage for rabbits, rodents, and small mammals:

a) Rabbits: 8-16 mg/kg daily dose (may divide into q8h-q24h) SC, IM or IV Increased efficacy and decreased toxicity if given once daily. If given IV, dilute into 4 mL/kg of saline and give over 20 minutes. ()

b) Rabbits: 5-10 mg/kg SC, IM, IV divided q8-24h Guinea pigs: 10-15 mg/kg SC, IM, IV divided q8-24h Chinchillas: 10-15 mg/kg SC, IM, IV divided q8-24h Hamster, rats, mice: 10 mg/kg SC, IM q12h Prairie Dogs: 5 mg/kg SC, IM q12h ()

c) Chinchillas: 2-5 mg/kg SC, IM q8- 12h ()

Amikacin Sulfate dosage for cattle:

For susceptible infections:

a) 10 mg/kg IM q8h or 25 mg/kg q12h ()

b) 22 mg/kg/day IM divided three times daily ()

Amikacin Sulfate dosage for horses:

For susceptible infections:

a) 21 mg/kg IV or IM once daily (q24h) ()

b) In neonatal foals: 21 mg/kg IV once daily ()

c) In neonatal foals: Initial dose of 25 mg/kg IV once daily; strongly recommend to individualize dosage based upon therapeutic drug monitoring. ()

d) Adults: 10 mg/kg IM or IV once daily (q24h)

Foals (<30 days old): 20-25 mg/kg IV or IM once daily (q24h).

For uterine infusion:

a) 2 grams mixed with 200 mL sterile normal saline (0.9% sodium chloride for injection) and aseptically infused into uterus daily for 3 consecutive days (Package insert; Amiglyde-V — Fort Dodge)

b) 1-2 grams IU ()

For intra-articular injection as adjunctive treatment of septic arthritis in foals:

a) If a single joint is involved, inject 250 mg daily or 500 mg every other day; frequency is dependent upon how often joint lavage is performed. Use cautiously in multiple joints as toxicity may result (particularly if systemic therapy is also given). ()

For regional intravenous limb perfusion (RILP) administration in standing horses:

a) Usual dosages range from 500 mg-2 grams; dosage must be greater than 250 mg when a cephalic vein is used for perfusion and careful placement of tourniquets must be performed. ()

Amikacin Sulfate dosage for birds:

For susceptible infections:

a) For sunken eyes/sinusitis in macaws caused by susceptible bacteria: 40 mg/kg IM once or twice daily. Must also flush sinuses with saline mixed with appropriate antibiotic (10-30 mL per nostril). May require 2 weeks of treatment. ()

b) 15 mg/kg IM or SC q12h ()

c) For gram-negative infections resistant to gentamicin: Dilute commercial solution and administer 15-20 mg/kg (0.015 mg/g) IM once a day or twice a day ()

d) Ratites: 7.6-11 mg/kg IM twice daily; air cell: 10-25 mg/egg; egg dip: 2000 mg/gallon of distilled water pH of 6 ()

Amikacin Sulfate dosage for reptiles:

For susceptible infections:

a) For snakes: 5 mg/kg IM (forebody) loading dose, then 2.5 mg/kg q72h for 7-9 treatments. Commonly used in respiratory infections. Use a lower dose for Python curtus. ()

b) Study done in gopher snakes: 5 mg/kg IM loading dose, then 2.5 mg/kg q72h. House snakes at high end of their preferred optimum ambient temperature. ()

c) For bacterial shell diseases in turtles: 10 mg/kg daily in water turtles, every other day in land turtles and tortoises for 7-10 days. Used commonly with a beta-lactam antibiotic. Recommended to begin therapy with 20 mL/kg fluid injection. Maintain hydration and monitor uric acid levels when possible. ()

d) For Crocodilians: 2.25 mg/kg IM q 72-96h ()

e) For gram-negative respiratory disease: 3.5 mg/kg IM, SC or via lung catheter every 3-10 days for 30 days. ()

Amikacin Sulfate dosage for fish:

For susceptible infections:

a) 5 mg/kg IM loading dose, then 2.5 mg/kg every 72 hours for 5 treatments. ()


■ Efficacy (cultures, clinical signs, WBC’s and clinical signs associated with infection). Therapeutic drug monitoring is highly recommended when using this drug systemically. Attempt to draw samples at 1,2, and 4 hours post dose. Peak level should be at least 40 mcg/mL and the 4-hour sample less than 10 mcg/mL.

■ Adverse effect monitoring is essential. Pre-therapy renal function tests and urinalysis (repeated during therapy) are recommended. Casts in the urine are often the initial sign of impending nephrotoxicity.

■ Gross monitoring of vestibular or auditory toxicity is recommended.

Client Information

■ With appropriate training, owners may give subcutaneous injections at home, but routine monitoring of therapy for efficacy and toxicity must still be done

■ Clients should also understand that the potential exists for severe toxicity (nephrotoxicity, ototoxicity) developing from this medication

■ Use in food producing animals is controversial as drug residues may persist for long periods

Chemistry / Synonyms

A semi-synthetic aminoglycoside derived from kanamycin, amikacin occurs as a white, crystalline powder that is sparingly soluble in water. The sulfate salt is formed during the manufacturing process. 1.3 grams of amikacin sulfate is equivalent to 1 gram of amikacin. Amikacin may also be expressed in terms of units. 50,600 Units are equal to 50.9 mg of base. The commercial injection is a clear to straw-colored solution and the pH is adjusted to 3.5-5.5 with sulfuric acid.

Amikacin sulfate may also be known as: amikacin sulphate, amikacini sulfas, or BB-K8; many trade names are available.

Storage / Stability/Compatibility

Amikacin sulfate for injection should be stored at room temperature (15 – 30°C); freezing or temperatures above 40°C should be avoided. Solutions may become very pale yellow with time but this does not indicate a loss of potency.

Amikacin is stable for at least 2 years at room temperature. Autoclaving commercially available solutions at 15 pounds of pressure at 120°C for 60 minutes did not result in any loss of potency.

Note: When given intravenously, amikacin should be diluted into suitable IV diluent etc. normal saline, D5W or LRS) and administered over at least 30 minutes.

Amikacin sulfate is reportedly compatible and stable in all commonly used intravenous solutions and with the following drugs: amobarbital sodium, ascorbic acid injection, bleomycin sulfate, calcium chloride/gluconate, cefoxitin sodium, chloramphenicol sodium succinate, chlorpheniramine maleate, cimetidine HCl, clindamycin phosphate, colistimethate sodium, dimenhydrinate, diphenhydramine HCl, epinephrine HCl, ergonovine maleate, hyaluronidase, hydrocortisone sodium phosphate/succinate, lincomycin HCl, metaraminol bitartrate, metronidazole (with or without sodium bicarbonate), norepinephrine bitartrate, pentobarbital sodium, phenobarbital sodium, phytonadione, polymyxin B sulfate, prochlorperazine edisylate, promethazine HCL, secobarbital sodium, sodium bicarbonate, succinylcholine chloride, vancomycin HCL and verapamil HCL.

The following drugs or solutions are reportedly incompatible or only compatible in specific situations with amikacin: aminophylline, amphotericin B, ampicillin sodium, carbenicillin disodium, cefazolin sodium, cephalothin sodium, cephapirin sodium, chlorothiazide sodium, dexamethasone sodium phosphate, erythromycin gluceptate, heparin sodium, methicillin sodium, nitrofurantoin sodium, oxacillin sodium, oxytetracycline HCL, penicillin G potassium, phenytoin sodium, potassium chloride (in dextran 6% in sodium chloride 0.9%; stable with potassium chloride in “standard” solutions), tetracycline HCL, thiopental sodium, vitamin B-complex with C and warfarin sodium. Compatibility is dependent upon factors such as pH, concentration, temperature and diluent used; consult specialized references or a hospital pharmacist for more specific information.

In vitro inactivation of aminoglycoside antibiotics by beta-lac-tam antibiotics is well documented. While amikacin is less susceptible to this effect, it is usually recommended to avoid mixing these compounds together in the same syringe or IV bag unless administration occurs promptly. See also the information in the Amikacin Sulfate Interaction and Amikacin Sulfate/Lab Interaction sections.

Dosage Forms / Regulatory Status

Veterinary-Labeled Products:

Amikacin Sulfate Injection: 50 mg (of amikacin base) per mL in 50 mL vials; Amiglyde-V (Fort Dodge), AmijectD (Butler), Amikacin K-9 (RXV), Amikacin C (Phoenix), Amtech Amimax C (IVX), Caniglide (Vedco); generic (VetTek); (Rx); Approved for use in dogs.

Amikacin Sulfate Intrauterine Solution: 250 mg (of amikacin base) per mL in 48 mL vials; Amifuse E (Butler), Amiglyde-V (Fort Dodge), Amikacin E (Phoenix), Amikacin E (RXV), Amtech Amimax E (IVX), Equi-phar Equiglide (Vedco); (Rx); Approved for use in horses not intended for food.

WARNING: Amikacin is not approved for use in cattle or other food-producing animals in the USA. Amikacin Sulfate residues may persist for long periods, particularly in renal tissue. For guidance with determining use and withdrawal times, contact FARAD (see Phone Numbers & Websites in the appendix for contact information).

Human-Labeled Products:

Amikacin Injection: 50 mg/mL and 250 mg/mL in 2 mL and 4 mL vials and 2 mL syringes; Amikin (Apothecon); generic; (Rx)



Thoracic Ultrasonography

Thoracic ultrasonography currently is regarded as the preferred method to diagnose pleuropneumonia in the horse. Although the value of the art of thoracic auscultation and percussion should not be undermined, clinicians managing horses with thoracic disease recognize the limitations of these tools. With the widespread use of thoracic ultrasound, the equine practitioner currently has the ability to determine the presence of pleuropneumonia and the location and the extent of the disease. Although sector scanners are superior (preferably 3.5- to 5.0-MHz transducers), linear probes also can be used to evaluate the thorax in practice.

Thoracic ultrasonography in horses with pleuropneumonia allows the clinician to characterize the pleural fluid and to evaluate the severity of the underlying pulmonary disease. The appearance of the pleural fluid may range from anechoic to hypoechoic, depending on the relative cellularity (). This fluid usually is found in the most ventral portion of the thorax and causes compression of normal healthy lung parenchyma with retraction of the lung toward the pulmonary hilus. The larger the volume of the effusion is, the greater the amount of compression atelectasis and lung retraction that occurs.

The presence of adhesions, pleural thickening, pulmonary necrosis, and compression atelectasis also can be detected. Fibrin has a filmy to filamentous or frondlike appearance and is usually hypoechoic (). Fibrin deposited in layers or in weblike filamentous strands on surfaces of the lung, diaphragm, pericardium, and inner thoracic wall limits pleural fluid drainage. Dimpling of the normally smooth pleural surface results in the appearance of “comettail” artifacts, created by small accumulations of exudate, blood, mucus, or edema fluid. Pulmonary consolidation varies from dimpling of the pleural surface to large, wedge-shaped areas of sonolucent lung ().

Atelectatic lung is sonolucent and appears as a wedge of tissue floating in the pleural fluid. Necrotic lung appears gelatinous and lacks architectural integrity. Peripheral lung abscesses are identified ultrasonographically by their cavitated appearance and the absence of any normal pulmonary structures (vessels or bronchi) detected within. Although detection of a pneumothorax may be easy for the experienced ultrasonagrapher, it is not as easy for the less experienced. The gas-fluid interface can be imaged through simultaneous movement in a dorsal to ventral direction with respiration, the “curtain sign” reproducing the movements of the diaphragm. The dorsal air echo moves ventrally during inspiration, similar to the lowering of a curtain, gradually masking the underlying structures. A pneumothorax without pleural effusion is even more difficult to detect ultrasonographically. Although free bright gas echoes within the pleural fluid can occur after thoracentesis, they are more often seen with anaerobic infections or when sufficient necrosis has occurred in a segment of parenchyma to erode into an airway and form a bronchopleural fistula (). The absence of gas echoes in pleural fluid does not rule out the possibility that anaerobic infection may be present.

Ultrasonography is a valuable diagnostic aid in the evaluation of the pleura, lung, and mediastinum of horses with pleuropneumonia. The detection and further characterization of the above abnormalities improve the clinician’s ability to form a more accurate prognosis. Adhesions can be detected that ultimately may affect the horse’s return to its previous performance level.

Horses with compression atelectasis and a nonfibrinous pleuritis have an excellent prognosis for survival and return to performance. The detection of areas of consolidation, pulmonary necrosis, or abscesses increases the probable treatment and recovery time, and the prognosis for survival decreases as these areas become more extensive. Ultrasonography can be used as a guide to sample or drain the area with a large fluid accumulation or the least loculation. These patients often benefit from progressive scanning to assess response to treatment and the need for drainage.

Pleural Drainage

After selection of an appropriate antimicrobial agent, the next decision to be made is whether to drain the pleural space. Ideally the decision is based on an examination of the pleural fluid. If the pleural fluid is thick pus, drainage using a chest tube should be initiated. If the pleural fluid is not thick pus, but the Gram’s stain is positive and white blood cell (WBC) counts are elevated, pleural drainage is recommended. Another indication for therapeutic thoracocentesis is the relief of respiratory distress secondary to a pleural effusion.

Many options exist for thoracic drainage, including intermittent chest drainage, use of an indwelling chest tube, pleural lavage, pleuroscopy and debridement, open chest drainage/debridement with or without rib resection in the standing horse, open chest drainage/debridement under general anesthesia, and lung resection under general anesthesia. Drainage of a pleural effusion can be accomplished by use of a cannula, indwelling chest tubes, or a thoracostomy. Thoracostomy is reserved for severe abscessation of the pleural space. Thoracocentesis is accomplished easily in the field and may not need to be repeated unless considerable pleural effusion reaccumulates.

Indwelling chest tubes are indicated when continued pleural fluid accumulation makes intermittent thoracocentesis impractical. If properly placed and managed, indwelling chest tubes provide a method for frequent fluid removal and do not exacerbate the underlying pleuropneumonia or increase the production of pleural effusion. The chest entry site and end of the drainage tube must be maintained aseptically. A one-way flutter valve may be attached to allow for continuous drainage without leakage of air into the thorax. If a chest tube is placed aseptically and managed correctly, it can be maintained for several weeks. It should be removed as soon as it is no longer functional. Heparinization of tubing after drainage helps maintain patency. Local cellulitis may occur at the site of entry into the chest but is considered a minor complication. Bilateral pleural fluid accumulation requires bilateral drainage in most horses.

Open drainage or thoracostomy may be considered when tube drainage is inadequate. Open drainage should not begin too early in the disease. An incision is made in the intercostal space exposing the pleural cavity and causing a pneumothorax. If the inflammatory process has fused the visceral and parietal pleura adjacent to the drainage site, a pneumothorax may not develop. The wound is kept open for several weeks while the pleural space is flushed and treated as an open draining abscess.

Pleural Lavage

Pleural lavage may be helpful to dilute fluid and remove fibrin, debris, and necrotic tissue. Lavage apparently is most effective in subacute stages of pleuropneumonia before loculae develop; however, pleural lavage may help break down fibrous adhesions and establish communication between loculae. Care must be exercised that infused fluid communicates with the drainage tube. Lavage involves infusing fluid through a dorsally positioned tube and draining it through a ventrally positioned tube (). In addition, 10 L of sterile, warm lactated Ringer’s solution is infused into each affected hemithorax by gravity flow. After infusion, the ventrally placed chest tube is opened and the lavage fluid is allowed to drain. Pleural lavage probably is contraindicated in horses with bronchopleural communications because it may result in spread of septic debris up the airways. Coughing and drainage of lavage fluid from the nares during infusion suggest the presence of a bronchopleural communication.

Differentiation From Neoplasia

Although pleuropneumonia is the most common cause of pleural effusion in the horse, the second most common cause is neoplasia. Differentiating between the two conditions is a challenge for the equine clinician because similarities exist in the clinical signs and physical examination findings.

Pleuropneumonia effusions are more likely to have abnormal nucleated cell count more than 10,000/μl (usually >20,000/μl) with reater than 70% neutrophils. Bacteria frequently are seen both intra- and extracellularly. A putrid odor may be present.

Neoplastic effusions have variable nucleated cell count. If caused by lymphosarcoma, abnormal lymphocytes may predominate. However, neoplastic cell often are not readily apparent and a definitive diagnosis may be difficult. Rarely do neoplastic effusions have a putrid odor. Bacteria are seen rarely in the cytology preparations.

Once again, use of ultrasonography helps determine if neoplasia is responsible for the effusion. Fibrin most commonly is detected in association with pleuropneumonia but has been detected in horses with thoracic neoplasia. Mediastinal masses associated with neoplasia may be readily visible (). Abnormal solitary masses on the lung surface may be visible in horses with metastatic neoplastic disease.

Comprehensive Management

The primary goals in managing a horse with pleuropneumonia are to stop the underlying bacterial infection, remove the excess inflammatory exudate from the pleural cavity, and provide supportive care. Ideally an etiologic agent is identified from either the tracheobronchial aspirate or pleural fluid and antimicrobial sensitivity determined. Without bacterial culture results, broad-spectrum antibiotics should be used because many horses have mixed infections of both gram-positive and gram-negative and aerobic and anaerobic organisms. Commonly used therapy is penicillin combined with an aminoglycoside such as gentamicin, enrefloxacin, trimethoprim and sulfamethoxazole, or chloramphenicol. Because of the need for long-term therapy, initial intravenous or intramuscular antimicrobials may need to be followed by oral antimicrobials. Preferably the oral antimicrobials are not administered until the horse’s condition is stable and improving because blood levels obtained by this route are not as high as those achieved by use of intramuscular or intravenous administration.

Treatment of anaerobic pleuropneumonia is usually empiric because antimicrobial susceptibility testing of anaerobes is difficult due to their fastidious nutritive and atmospheric requirements. Thus familiarity with antimicrobial susceptibility patterns is helpful in formulating the treatment regimen when an anaerobe is suspected. The majority of anaerobic isolates are sensitive to relatively low concentrations (22,000 IU/kg IV q6h) of aqueous penicillin. Bacteroides fragilis is the only frequently encountered anaerobe that is routinely resistant to penicillin, although other members of the Bacteroides family are known to produce B lactamases and are potentially penicillin-resistant.

Chloramphenicol (50 mg/kg PO q4h) is effective against most aerobes and anaerobes that cause equine pleuropneumonia. However, because of human health concerns the availability of chloramphenicol may decrease. Metronidazole has in vitro activity against a variety of obligate anaerobes including B. fragilis. Pharmacokinetic studies indicate a dose of 15 mg/kg intravenously or orally four times a day is necessary to maintain adequate serum levels. Oral administration rapidly results in adequate serum levels and thus is an acceptable route of administration for horses with pleuropneumonia. Metronidazole is not effective against aerobes and therefore always should be used in combination therapy at a dose of 15 mg/kg every 6 to 8 hours. Side effects of metronidazole include loss of appetite and lethargy; use of the drug should be halted when these signs are observed. Aminoglycosides and enrofloxacin should not be considered for the treatment of pleuropneumonia caused by an anaerobe unless these drugs are used in combination therapy with penicillin.

Ancillary Treatment

Antiinflammatory agents help reduce pain and may decrease the production of pleural fluid. This in turn may encourage the horse to eat and maintain body weight. Flunixin meglumine (500 mg ql2-24h) or phenylbutazone (1-2 g q12h) is commonly used for this purpose. In this author’s opinion, corticosteroids are contraindicated for the treatment of bacterial pleuropneumonia. Rest and the provision of an adequate diet are important components of the treatment of pleuropneumonia. Because the disease course and period of treatment are usually prolonged, attempts should be made to encourage eating. Intravenous fluids may be indicated in the acute stages of the disease to treat dehydration resulting from anorexia and third-space losses into the thorax.

Veterinary Medicine


1. What is the typical signahnent for acute colitis?

• German shepherds and golden retrievers are the most commonly affected breeds.

• 1-4 years old is the most common age.

• Males are more commonly affected than females (3:2).

2. What are the common clinical signs of acute colitis?

• Diarrhea or soft stool (watery, mucus, fresh blood, frequent small amounts)

• Tenesmus

• Normal appetite with little or no weight loss

• Vomiting (30%)

• Abdominal pain

3. What is the typical scenario for a nosocomial clostridial infection?

Acute, bloody diarrhea beginning 1-3 days after exposure to a veterinary hospital.

4. What are the possible causes of acute colitis?

The cause of acute colitis is usually unknown, but the following possibilities should be considered:

1. Mucosal injury by a foreign body or trauma

2. Infection

• Parasitic (whipworms[Trichuris sp.])

• Bacterial (Salmonella, Campylobacter, Clostridium spp.)

• Fungal (histoplasmosis)

3. Systemic disease (especially uremia)

5. What differential diagnoses should be considered in patients suspected of acute colitis?

1. Other gastrointestinal problems

• Chronic colitis

• Neoplasia (adenocarcinoma, lymphoma, leiomyosarcoma, polyp)

• Ileocolic intussusception

• Cecal inversion

• Irritable colon (diagnosis by exclusion)

• Rectal stricture

• Perianal fistula

• Uremic ulcers

2. Painful abdomen

• Hemorrhagic gastroenteritis (HGE)

• Viral enteritis

• GI foreign bodies

• Bowel ischemia due to thrombi

• Intestinal volvulus

• Pancreatitis

• Hepatobiliary problems

• Urologic disorder (renal calculi, pyelonephritis, urinary tract infection)

• Peritonitis (ruptured abdominal organ, sepsis)

• Splenic torsion

• Genital problems (uterine torsion or rupture, testicular torsion, prostatic abscess)

3. Thoracolumbar pain

6. Which diagnoses are most commonly confused with acute colitis?

• Neoplasia (adenocarcinoma, lymphoma, leiomyosarcoma, polyps)

• Rectal stricture

7. What are the most common physical findings?

1. Physical examination is usually normal.

2. Deep palpation may or may not produce abdominal pain.

3. Rectal examination may be painful and show fresh blood and mucus.

8. How do you approach the diagnosis of acute colitis?

• Rectal examination

• Fecal flotation for ova or parasites

• Direct and stained fecal smears

• Fecal culture

• Routine laboratory evaluation (complete blood count, biochemical profile, urinalysis)

• Abdominal radiographs and barium enema

• Colonoscopy

• Mucosal biopsy via colonoscopy

9. Describe the appropriate symptomatic treatment.

1. Withhold food for 24-48 hours or until diarrhea resolves. If lymphocytic-plasmocytic enteritis is suspected, withholding food will not resolve the problem.

2. Give crystalloid fluids with potassium chloride.

3. Give medication to decrease fecal water and increase colonic motility (loperamide).

10. What cause-specific treatments may be used for acute colitis?

• Correction of underlying cause if known (e.g., foreign body removal)

• Reduction of clostridial overgrowth (tylosin preferred; also metronidazole)

• Treatment of inflammatory bowel disease (i.e., chronic colitis) with tylosin, mesalazine, sulfasalazine (oral, enema, or foam), or prednisone (antiinflammatory doses)

• High-fiber diet (often supplemented with Metamucil)

Veterinary Medicine

Hepatic Lipidosis And Acute Hepatitis

1. What is hepatic lipidosis?

Hepatic lipidosis is a common disease of cats in which excessive fat accumulates in hepatocytes and may lead to severe intrahepatic cholestasis and progressive liver failure. Most cases in cats are idiopathic. Diabetes mellitus, pancreatitis, cholangiohepatitis, hyperthyroidism, hypertrophic cardiomyopathy, renal disease, chronic cystitis, chronic upper respiratory infections, hyperadrenocorticism, and neoplasia also have been detected in some cats with hepatic lipidosis. Most dogs with hepatic lipidosis have another underlying disease process.

2. What is acute hepatitis?

Acute hepatitis refers to any condition that causes inflammation and swelling of the liver. Injury may be precipitated by drugs, trauma, toxins, and infectious agents. In addition, immune-mediated diseases, inborn errors of metabolism (copper toxicity in Bedlington terriers is an example), and neoplastic diseases may result in acute hepatitis. Acute hepatitis also accompanies acute pancreatitis in both dogs and cats.

3. What historical questions should be asked of clients with animals with suspected acute hepatitis?

Drug administration, trauma, and toxin exposure should be ruled out by history. Many drugs, including potentiated sulfonamides, carprofen, anthelmintics such as metronidazole, and benzodiazepines have been associated with acute hepatitis or acute hepatic necrosis. It should be determined whether the animal has ingested moldy food; aflatoxins produced by some fungi are potent hepatotoxins. Travel and vaccination histories are important; leptospirosis may result in acute hepatitis in dogs and is a direct zoonosis.

4. What population of cats typically develops idiopathic hepatic lipidosis?

Middle-aged cats are primarily affected, but cats of any age may develop hepatic lipidosis. There does not appear to be a breed or sex predisposition. A large percentage of affected cats are obese before onset of clinical signs.

5. What historical complaints are commonly associated with acute hepatitis or lipidosis?

Anorexia occurs in most animals. In cats with idiopathic lipidosis, a stressful episode such as surgery, boarding, moving, or a new member in the household may precede appetite loss. Lethargy, depression, icterus, ptyalism, and vomiting are also commonly reported with acute hepatic diseases. Diarrhea is uncommon with idiopathic lipidosis but occurs in some animals with acute hepatitis. Hepatic encephalopathy (HE), characterized by head pressing, stupor, and coma, occurs in some animals with acute hepatic diseases.

6. What physical abnormalities are commonly detected in animals with acute hepatitis or lipidosis?

Depression, icterus, and dehydration are common. At presentation, most cats with idiopathic hepatic lipidosis have lost as much as 25-50% of their previous body weight. Most animals with acute hepatitis have clinical signs of shock, including elevated heart rate, pale mucous membranes, increased capillary refill time, and weak pulse. Liver size may be normal, increased, or decreased, depending on the primary cause and duration of the disease process before acute presentation. Animals with chronic hepatic disease that present with an acute exacerbation may have abdominal distention due to sustained portal hypertension or hypoalbuminemia-associated transudative ascites.

7. What diagnostic tests should be considered for animals with suspected acute hepatitis or lipidosis?

Complete blood count, platelet count, serum biochemistry panel, activated clotting time, and urinalysis should be assessed on admission. Packed cell volume, total protein, blood glucose, electrolytes, and coagulation should be assessed as soon as possible and emergency treatment initiated as indicated. Coagulation should be assessed because hepatic aspiration or biopsy is often indicated and disseminated intravascular coagulation is common, particularly in animals with acute hepatitis.

8. What routine laboratory abnormalities are most consistent with acute hepatitis or lipidosis?

Although no pathognomonic changes in complete blood count are associated with hepatic lipidosis, mild nonregenerative anemia, neutrophilia, or neutropenia may be noted. Increases in liver enzyme activities are common; any combination of increased activity of alanine transferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or gamma-glutamyl transferase (GGT) may occur. In most cats, increases in ALP and GGT activities are greater than increases in ALT and AST activities. Lack of increased liver enzyme activities does not exclude the diagnosis of idiopathic hepatic lipidosis. Hyperbilirubinemia and bilirubinuria occur in most cats with idiopathic hepatic lipidosis. Findings are similar with acute hepatitis, but increases in alanine transferase and aspartate aminotransferase activities are usually greater than increases in alkaline phosphatase and gamma-glutamyl transferase activities.

9. What ancillary diagnostic tests help to determine the cause of liver disease in animals with suspected acute hepatitis or lipidosis?

Fasting and postprandial serum bile acids are usually markedly increased but do not need to be measured if hyperbilirubinemia is present. Fasting serum ammonia concentrations may be elevated and can be used for indirect assessment of the presence of hepatic encephalopathy. Abdominal radiographs, hepatic ultrasound, pancreatic ultrasound and trypsin-like immunoreactivity (TL1) tests may be used to narrow the differential list in animals with acute hepatic disease.

10. Do I need to perform a hepatic biopsy for all animals with suspected acute hepatitis or lipidosis?

A presumptive diagnosis of idiopathic hepatic lipidosis in cats may be made by the combination of appropriate history, laboratory abnormalities, and vacuolated hepatocytes on cytologic evaluation of a fine aspirate of the liver. If the cause of hepatitis is determined by history (trauma, drugs, toxins) or other findings (pancreatitis), biopsy may not be needed. However, the reference test for hepatic diseases is hepatic histologic evaluation. If hepatic aspiration or biopsy is performed, samples should be cultured for aerobic and anaerobic bacteria.

11. What immediate supportive care should be provided to animals with suspected acute hepatitis or lipidosis?

Fluid, electrolyte, acid-base, coagulation, and glucose abnormalities should be corrected as discussed in other chapters. Depending on acid-base and electrolyte status, 0.45% NaCl and 2.5% dextrose or Normosol-R are appropriate fluid choices. Potassium supplementation is required for most cases. Antibiotics should be administered to all animals with suspected acute hepatitis because bacterial translocation from the intestines into the liver is common. Penicillin derivatives or first-generation cephalosporins administered parenterally are adequate if clinical findings of sepsis are not present. Enrofloxacin should be considered in animals with suspected gram-negative sepsis. Vitamin K should be given subcutaneously to animals with increased activated clotting time. Supplementation with B vitamins is suggested for most cases. Hepatic encephalopathy, if present, is managed as described for portosystemic shunts (see chapter 83). Appetite stimulants, including cyproheptadine and benzodiazepams, generally are not successful alone. Benzodiazepams may lead to severe sedation if hepatic dysfunction is severe and have been associated with liver failure.

Whether enteral feeding is indicated depends on the cause of the disease. Early, aggressive nutritional therapy is the key to successful treatment of idiopathic hepatic lipidosis in cats. Initial short-term nutritional support may be provided by a nasoesophageal tube. However, because nutritional support is required for at least 3-6 weeks in most cases, a gastrostomy tube is strongly recommended. Multiple small meals should be fed to cats to provide a total of 60-80 kcal/kg/day. Most full-grown cats can handle 50-80 ml of food per feeding when the volume of food at each meal is gradually increased over several days. Protein should not be restricted unless signs of hepatic encephalopathy are present. Food should always be offered by mouth; the tube can be pulled after eating begins and liver enzymes have returned to normal.

12. What is the prognosis for recovery from idiopathic hepatic lipidosis?

The prognosis is guarded to fair, depending on how early the disease is recognized. The conditions can be reversed with aggressive nutritional therapy. Owners must be counseled that recovery may require up to 20 weeks before spontaneous eating occurs. Without treatment, hepatic lipidosis is usually fatal, leading to progressive liver failure.

Veterinary Medicine

Portosystemic Shunts

1. What is a portosystemic shunt?

A portosystemic shunt is an abnormal vessel that connects the portal vein to a systemic vein. The most common locations for portosystemic shunts are a patent ductus venosus or a connection between the portal vein and caudal vena cava or azygous vein. Single extraheptic shunts are most common in small-breed dogs and cats, whereas single intrahepatic shunts are most common in large-breed dogs.

2. What is the difference between congenital and acquired portosystemic shunts?

Most acquired shunts are multiple and extrahepatic. Acquired shunts develop because of sustained portal hypertension from chronic liver disease and cirrhosis. Congenital portosystemic shunts are usually single and may be intra- or extrahepatic. The most common intrahepatic portosystemic shunt is a patent ductus venosus.

3. Are certain breeds associated with portosystemic shunts?

Congenital portosystemic shunts may occur in any breed of dog but are common in miniature schnauzers, miniature poodles, Yorkshire terriers, dachshunds, Doberman pinschers, golden retrievers, Labrador retrievers, and Irish setters. There are affected lines in miniature schnauzers, Irish wolfhounds, Old English sheepdogs, and Cairn terriers. Mixed breed cats are more commonly affected than purebred cats, but Himalayans and Persians seem to overrepresented as purebreds. Acquired portosystemic shunts are secondary to chronic hepatic disease and so may occur in any breed.

4. Where are most portosystemic shunts located?

Single extrahepatic shunts most commonly connect the portal vein (or the left gastric or splenic vein) with the caudal vena cava cranial to the phrenicoabdominal vein. Single intrahepatic shunts can be a communication of the portal vein to the caudal vena cava which is a failure of the ductus venosus to close. Shunts in the right medial or lateral liver lobes occur with an unknown pathogenesis.

5. Why do patients with portosystemic shunts have decreased liver function?

Portal venous blood is important because it brings hepatotropic growth factors and insulin to the liver. If insulin bypasses the liver in a shunt, significant quantities are utilized by other organs and the liver receives less benefit. Portal venous blood flow is important for normal liver development as well as glycogen storage, hypertrophy, hyperplasia, and regeneration. Congenital portosystemic shunts are often associated with hepatic atrophy, hypoplasia, and dysfunction.

6. What are the most common clinical signs of portosystemic shunts?

Failure to thrive and failure to gain weight are appropriately common. Most clinical signs are referable to hepatic encephalopathy, which is defined as clinical signs of neurologic dysfunction secondary to hepatic disease. Signs include ataxia, stupor, lethargy, unusual behavior, disorientation, blindness, and seizures. Some animals display anorexia, vomiting, and diarrhea. Polyuria and polydipsia may be present. Some animals have ammonium biurate urolithiasis, which may result in pollakiuria, hematuria, stranguria, or obstruction. Increased production of saliva (ptyalism) and abdominal distention due to ascites occur in some animals. Ptyalism is more common in cats.

7. What causes hepatic encephalopathy associated with portosystemic shunts?

Products of bacterial metabolism in the intestine, such as ammonia, short-chain fatty acids (SCFAs), mercaptans, gamma-aminobutyric acid (GABA), and endogenous benzodiazepines have been suggested as mediators of hepatic encephalopathy. In addition, the ratio of aromatic amino acids to branched-chain amino acids is often increased in patients with portosystemic shunts. The aromatic amino acids may act as false neurotransmitters. Phenylalanine and tyrosine may act as weak neurotransmitters in the presynaptic neurons of the CNS. Tryptophan causes increased production of serotonin, which is a potent inhibitory neurotransmitter. The GABA receptor has binding sites for barbiturates, benzodiazepines, and substances with similar chemical structure to benzodiazepines. These agents may be responsible for depression of the CNS in hepatic encephalopathy.

8. What factors may precipitate an hepatic encephalopathy crisis?

A protein rich meal, gastrointestinal bleeding associated with parastites, ulcers or drug therapy; administration of methionine- containing urinary acidifiers; or lipotropic agents may precipitate a crisis. Blood transfusions with stored blood may also contribute to a crisis as the ammonia levels can be high in the stored blood.

9. How is hepatic encephalopathy treated?

The animal should be evaluated for hypoglycemia immediately and treated appropriately if it is present. Appropriate fluid therapy based on acid-base and electrolyte status (see chapter 81) should be initiated to correct abnormalities. LRS should be avoided. Hypoglycemia, alkalosis, hypokalemia, and gastrointestinal bleeding should be identified and corrected. Ammonia concentration and production should be decreased by administering lactulose and neomycin (10-20 mg/kg orally every 6 hr) if a swallow response is present. Oral metronidazole may be used at a dose of 10 mg/kg every 8 hr in place of neomycin. If the animal is comatose, 20-30 ml/kg of lactulose diluted 1:2 with water or a 1:10 dilution of povidone-iodine solution may be given as an enema. Seizures may be treated initially with elimination of ammonia by enemas as listed above. Oral loading doses of potassium bromide may be useful. If seizures cannot be controlled, IV propofol as a constant rate infusion may be necessary, but respiratory support may be needed. Some animals with hepatic encephalopathy have difficulty in metabolizing benzodiazepines such as diazepam, which should be avoided. If these drugs do not control seizures, intravenous phenobarbital may be titrated slowly to effect. Patients often have decreased clearance of barbiturates.

10. What routine blood work and urinalysis abnormalities suggest portosystemic shunts?

Microcytosis is a consistent abnormality of complete blood cell count in animals with portosystemic shunts. Some animals manifest acid-base, electrolyte, and glucose disturbances (hypoglycemia). Because of vomiting and dehydration, prerenal azotemia may be present. There is no consistent finding with regard to alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum alkaline phosphatase (ALP); activities of these enzymes may be elevated, decreased, or normal in patients with portosystemic shunts. Hypoalbuminemia is common, as are coagulopathies. Some animals have isothenuric urine due to medullary wash-out; ammonium biurate crystals may be identified on microscopic examination of urine sediment.

11. What are the best ways to diagnose a portosystemic shunt?

Elevated serum pre- and postprandial bile acids in a young animal with signs of hepatic encephalopathy and stunted growth are consistent with but not diagnostic for portosystemic shunts. A nuclear medicine scan using transcolonic sodium pertechnetate Tc99m demonstrates radioactivity in the heart before the liver in an animal with portosystemic shunt. Nuclear medicine is rapid, noninvasive, and safe to the animal. The disadvantages are that the animal is radioactive for 24 hours, studies can be performed only by specially trained personnel, exact location of the shunt cannot be determined, and cases of hepatic microvascular dysplasia, which have shunting within the liver (as in Cairn terriers), may give false-negative results. When nuclear medicine facilities are unavailable, positive contrast portography may demonstrate the anomalous vessel. Portography, however, is technically demanding and invasive. Furthermore, a second surgical procedure is required to repair the shunt because of an otherwise dangerously long period of anesthesia. The major advantage of positive contrast portography is that it definitively locates the shunt.

12. What is the best way to manage a patient with portosystemic shunt?

Although medical management may be beneficial, surgical ligation of the shunt is optimal. In one study, animals that receive total ligation, even if it had to be done in two or more surgeries, showed more clinical improvement than patients with incomplete shunt ligation. In general, cats do not do as well with medical therapy.

13. Describe the preoperative management of a patient with portosystemic shunt.

In animals displaying hepatic encephalopathy, it is important to correct acid-base and electrolyte disturbances before surgery. Measures to control hepatic encephalopathy also should be performed before surgery, including a low protein diet, oral lactulose, and neomycin or metronidazole. A moderately protein-restricted diet with the bulk of calories coming from carbohydrates and fat is optimal. Vegetable and dairy proteins are better tolerated than meat and egg proteins. With each patient, the protein level should be increased to the maximum tolerated. Psyllium at 1-3 teaspoons per day has been advocated to help tolerance of proteins. Some have recommended supplementation with vitamins A, B, C, E, and K. Medical stabilization for 1-2 weeks before surgery is recommended for all patients with portosystemic shunts. A preoperative coagulation screen should be performed, and crossmatched fresh whole blood should be available. Fresh frozen plasma transfusions may be necessary for hypoalbuminemic patients. Most surgeons administer a broad-spectrum antibiotic (e.g., first-generation cephalosporin) intravenously before and during surgery.

14. What considerations must be given to drug therapy and anesthetic use in patients with portosystemic shunts?

Because liver function decreases in patients with portosystemic shunts, drugs that are potentially hepatotoxic should be avoided. In addition, hepatic clearance of drugs and anesthetic agents may be delayed.

15. What parameters should be monitored postoperatively in patients with portosystemic shunts?

After surgery, many patients with portosystemic shunts are hypoglycemic, hypothermic, and hypoalbuminemic. A postoperative database should include body weight, temperature, packed cell volume, total solids, and glucose. Additional useful information is provided by electrolytes and albumin. Maintaining hydration status and perfusion with a balanced electrolyte solution is important. Mucous membrane color, capillary refill time, pulse rate and quality, and temperature should be assessed, and the patient should be monitored for seizures. In addition, serial measurement of abdominal circumference is helpful because a number of patients develop portal hypertension and ascites postoperatively.

16. What are common postsurgical complications?

Sepsis, seizures, and portal hypertension are the most critical complications that may develop postoperatively, although pancreatitis and intussusceptions have been reported. Gastrointestinal hemorrhage also may result, which can precipitate a hepatic encephalopathy crisis. Animals with seizures should be treated with appropriate measures to normalize acid-base and electrolyte balance. Sepsis should be treated aggressively.

17. What are common signs of postoperative portal hypertension?

Portal hypertension most commonly results in abdominal distention secondary to ascites. In some cases, portal hypertension is subclinical and ascites resolves in several days. Some patients develop abdominal distention, pain, and hypovolemia; others have abdominal distention with severe pain, hypovolemia, cardiovascular collapse, hemorrhagic diarrhea, and septic or endotoxic shock.

18. How should postoperative portal hypertension be treated?

If the animal develops abdominal distention with no clinical signs of pain or discomfort, continued medical therapy is indicated. Most animals with pain and abdominal distention stabilize with colloid fluid therapy. Patients with severe pain, abdominal distention, bloody diarrhea, and cardiovascular shock should be treated for shock with fluids, stabilized as much as possible, and taken for exploratory surgery to remove the ligature or thrombus that has probably developed in a partially attenuated portosystemic shunt.

19. Why may a patient with portosystemic shunt become septic postoperatively?

A patient with portosystemic shunt may develop septic peritonitis postoperatively because of bacteremia in the portal vein. The monocyte-phagocyte system in the liver may not be fully functional. Sepsis may develop as a result of inadequate filtering of portal blood by the liver before the blood reaches the systemic circulation.

20. What is hepatic microvascular dysplasia?

Hepatic microvascular dysplasia is a congenital disorder with histologic vascular abnormalities that resemble those seen in portosystemic shunts.

21. Are there breed predispositions for hepatic microvascular dysplasia?

Cairn and Yorkshire terriers are most commonly affected with hepatic microvascular dysplasia. However, many other breeds, including dachshund, poodle, Shih Tzu, Lhasa Apso, cocker spaniel, and West Highland White terrier may be affected.

22. What are the clinical signs of hepatic microvascular dysplasia?

Clinical signs are not consistently seen, but in severe cases they are quite similar to those seen with portosystemic shunts. Hyperammonemia and ammonium biurate cystalluria rarely develop. A dog may have hepatic microvascular dysplasia with elevated bile acids but be sick for another cause.

23. When should hepatic microvascular dysplasia be considered as a differential diagnosis?

Hepatic microvascular dysplasia should be considered in a patient with clinical signs consistent with a portosystemic shunt, increased bile acid concentration, and consistent liver biopsy results. Scintigraphy is consistently normal.

24. What is the treatment for hepatic microvascular dysplasia?

Treatment should not be done if the patient is subclinical. If signs of hepatic encephalopathy are present, treatment is indicated as for patients with portosystemic shunts. It is unknown at this time whether subclinical patients will develop signs of disease.

Veterinary Medicine

Acute Pancreatitis

1. Compare acute and chronic pancreatitis.

Acute Chronic
Acute inflammatory condition Long-standing inflammation
No evidence of fibrosis Fibrosis and loss of acinar cell mass
Mild or severe Mild or severe
Reversible histopathologic changes Irreversible histopathologic changes


2. Describe the pathophysiology of severe pancreatitis.

Severe pancreatitis is characterized by extensive pancreatic necrosis and multiple organ involvement (perhaps even organ failure). The exocrine pancreas produces a number of digestive enzymes necessary for the degradation of proteins, fats, and polysaccharides. These enzymes are synthesized in inactive proenzyme forms that are activated only after they are secreted into the small intestine. In pancreatitis digestive enzymes are activated in the pancreas rather than the intestine because of damage to the gland or some stimulatory signal that results in pancreatic autodigestion. Systemic complications develop as activated pancreatic enzymes enter the bloodstream.

3. What is the most common cause of acute pancreatitis?

In most cases, the cause remains unknown. Causes that are often listed include nutrition (high fat meal), drugs (cholinesterase inhibitors and cholinergic agonists, thiazide diuretics, furosemide, estrogens, azathioprine, L-asparaginase, sulfonamides, tetracycline, metronidazole, cimetidine, ranitidine, acetaminophen, procainamide, and nitrofurantoin), organophosphates, trauma, hypoperfusion, hypercalcemia, hyperlipidemia (Schnauzers), and neoplastic infiltration by pancreatic adenocarcinoma. In cats, pancreatitis also is associated with concurrent hepatic lipidosis, infection with Toxoplasma gondii, and biliary tract inflammation.

4. Why is ingestion of a meal high in fat implicated as a cause of acute pancreatitis in dogs?

The pancreatic enzyme lipase metabolizes ingested triglycerides to free fatty acids in pancreatic capillaries. These fatty acids are directly injurious to the pancreas. The high incidence of pancreatitis in miniature Schnauzers also may be related to the high prevalence of familial hyperlipoproteinemia.

5. What are the primary presenting complaints and physical findings in dogs with pancreatitis?

Common clinical findings are vomiting, abdominal pain, dehydration, and fever. In dogs the duration of vomiting may be several days or, in acute hemorrhagic pancreatitis, only a few hours. Uncommon systemic complications include icterus, respiratory distress, and bleeding disorders.

6. Do cats present with the same symptoms as dogs?

Of interest, whereas vomiting is a common historical finding in dogs, most cats present with anorexia (97%), lethargy (100%), dehydration (92%), hypothermia (68%), vomiting (35%), abdominal pain (25%), a palpable abdominal mass (23%), respiratory distress (20%), ataxia (15%), and diarrhea (15%).

7. What are the radiographic signs of pancreatitis?

The most common radiographic finding is loss of visceral detail (ground-glass appearance) in the right cranial abdomen. Other radiographic signs include displacement of the descending duodenum to the right and of the stomach to the left, presence of a mass medial to the descending duodenum, and a gas-filled duodenum.

8. Describe the ultrasonic changes associated with pancreatitis.

Ultrasound changes include pancreatic swelling, increased echogenicity of the pancreas, and, less frequently, a mass effect in the area of the pancreas.

9. Are elevations in serum amylase and lipase activities definitive for the diagnosis of pancreatitis?

No. Neither enzyme is pancreas-specific; both are also produced by gastric and intestinal mucosal cells. Furthermore, because both enzymes are eliminated through the urine, a decrease in renal perfusion results in elevations of both enzymes. Finally, the administration of dexamethasone to dogs causes significant elevations in lipase without histologic evidence of pancreatitis.

10. Do normal lipase and amylase values eliminate the possibility of pancreatitis?

No. Many dogs and even more cats have confirmed pancreatitis with normal levels of both enzymes. Normal enzyme values in animals with pancreatitis may be due to impairment in pancreatic perfusion, depletion of stored enzymes, and / or disruption of the synthesis of new enzymes.

11. How is the diagnosis of pancreatitis confirmed?

Other than by histology, pancreatitis cannot be diagnosed on the basis of one test result. Common laboratory findings include leukocytosis, hyperglycemia, hypocalcemia, and elevations in amylase and lipase. Elevations in trypsin-like-immunoreactivity (TLI) correlate well with pancreatitis in both dogs and cats but also are affected by renal perfusion; furthermore, results generally take several days to return. Abdominal fluid analysis — in particular, lipase levels higher than serum lipase values — helps to make a case for pancreatitis. Ultrasound is useful for identifying an enlarged, inflamed pancreas. Diffuse or focal hypoechoic areas in the gland, along with compatible laboratory and physical findings, justify a high index of suspicion of pancreatitis.

12. How can the severity of acute pancreatitis be ascertained?

On admission it may not be easy to predict the severity or probable cause of acute pancreatitis. The clinician should be cognizant of concurrent laboratory abnormalities or clinical signs suggesting systemic complications. Examples include thrombocytopenia or clotting abnormalities, which may suggest disseminated intravascular coagulation (DIC); oliguria, which may indicate acute renal failure; hypotension and tachycardia, which may indicate systemic inflammatory response syndrome; and hypoglycemia, which may suggest sepsis.

13. What are the key components in treatment of pancreatitis?

The most important element of treatment is adequate fluid resuscitation. Decreased pancreatic perfusion due to hypovolemia, which may result from vomiting and third-space losses, may lead to progression of the disease if fluid therapy is inadequate. Recent studies suggest that colloid fluid resuscitation (plasma, hetastarch, and dextran 70) is an important component in the therapy of pancreatitis. In particular, fresh frozen plasma (10-20 ml / kg) is important in treatment of moderate-to-severe cases. Plasma as a colloid provides only small increases in oncotic properties but supplies clotting factors for management of disseminated intravascular coagulation and protease inhibitors that deactivate pancreatic enzymes in the systemic circulation. Prophylactic antibiotics, pain relief, antiemetics, and antacids are also important components of therapy. Studies in cats with experimentally induced acute hemorrhagic pancreatitis have shown that low-dose dopamine (5 mg / kg / min) reduces the severity of pancreatitis by reducing microvascular permeability. Dopamine as an adjunctive treatment awaits clinical evaluation.

14. How is fresh frozen plasma useful in the treatment of pancreatitis?

Studies in dogs suggest when alpha2-macroglobulin, one of the scavenger proteins for activated proteases in serum, is depleted, death rapidly ensues. Fresh frozen plasma (FFP) or fresh whole blood not only contains alpha2-macroglobulin but also albumin. Unfortunately, in a study of human pancreatitis patients, plasma failed to show any benefit. Incubating FFP with heparin may release antithrombin III and thus be useful in disseminated intravascular coagulation secondary to pancreatitis.

15. Is there evidence supporting the use of antibiotics or nonsteroidal antiinflammatory agents in pancreatitis?

No. Studies in humans have shown no benefit to antibiotics nor non-steroidal antiinflammatory agents. No data are available for the dog or cat.

16. What is the role of surgery in acute pancreatitis?

In most instances, pancreatitis is treated medically, and surgical intervention is not recommended. In patients that develop septic peritonitis or pancreatic abscess, however, surgery is the treatment of choice to remove necrotic tissue and to lavage the abdomen. Surgery also should be considered in patients who continue to deteriorate even with aggressive medical management.

17. What is done when the patient vomits every time food is offered?

Most patients with mild pancreatitis recover after avoidance of oral ingestion for 2 days, followed first by gradual introduction of water and then by small meals high in carbohydrates over the next few days. In patients that continue to vomit when offered food, one must first evaluate the case to ensure that no underlying disorder other than pancreatitis explains the persistent vomiting. In cases of smoldering pancreatitis, placement of a jejunostomy tube to provide nutrition with minimal stimulation of the pancreatitis should be strongly considered.

18. What are the long-term complications of pancreatitis?

Recurrent episodes of pancreatitis may result in progressive loss of pancreatic tissue and eventual development of diabetes mellitus and / or exocrine pancreatic insufficiency. Additional complications reported include acute fluid accumulation, infected necrosis, pancreatic pseudo-cyst formation, and pancreatic abscess.


19. Do corticosteroids cause severe pancreatitis?

Corticosteroids do not appear to cause pancreatitis, although they do increase serum lipase activity (but decrease serum amylase activity). Corticosteroid therapy is of no proven benefit in pancreatitis and may be harmful in severe pancreatitis.

20. Should food and water be withheld to allow the pancreas to rest and recover from the inflammatory episode?

Pancreatic rest has become the mainstay for treatment of acute pancreatitis, despite the absence of any clinical or experimental evidence to support this approach! Contrary to popular belief, pancreatic rest by avoiding pancreatic exocrine secretion has not made any impact on the clinical outcome of pancreatitis. Furthermore, no conclusive evidence to date indicates that medical treatment intended to decrease pancreatic exocrine secretion has any benefit, other than avoidance of pain, on the course of the disease. These observations are not surprising when one considers the fact that pancreatic exocrine secretion is severely impaired in an inflamed pancreas. If the pancreas is unable to respond to secretory stimuli, it makes perfect sense that therapeutic maneuvers to avoid pancreatic exocrine stimulation will have no bearing on the disease process.

21. Should total parenteral nutrition (TPN) be used in the treatment of pancreatitis?

In human patients, no difference in serum amylase activities between patients receiving total parenteral nutrition and controls is seen in the first 7 days after the diagnosis of acute pancreatitis. Although the total parenteral nutrition group achieved significantly greater nitrogen balance than controls, they also required significantly more days to first oral intake of clear liquids and full caloric intake. Most importantly, total parenteral nutrition patients experienced a significant prolongation of hospital stay (15 vs. 10 days in controls). No information is available in animals with pancreatitis.

22. Should total enteral nutrition (TEN) be used in the treatment of pancreatitis?

In human patients, total enteral nutrition moderates the acute-phase response and improves disease severity and clinical outcome despite unchanged pancreatic injury on computed tomography scan. Oxidant stress and systemic exposure to endotoxin also are reduced with total enteral nutrition. In humans, enteral feeding modulates the inflammatory and sepsis response in acute pancreatitis and is clinically beneficial. No information is available in animals with pancreatitis.



Balantidium coti

Balantidium coli is primarily a pathogen of sheep. Only one case report of natural infection in the dog has ever been published. In another report, a total of 375 fecal samples of 56 mammalian species belonging to 17 families of 4 orders were examined for the detection of Balantidium coli. B. coli organisms were detected in several animal species, but not in dogs or cats.

Entamoeba histolytica

Two isolated case reports of colitis in dogs and one in cats are associated with recovery of Entamoeba histolytica from the feces. E. histolytica can be recovered from the feces of healthy dogs and cats, but it appears to be of low pathogenicity in dogs and cats.


Giardia: Cause

Giardia spp. are protozoal parasites that primarily infect the small intestine of dogs and cats. The cecum and colon are only occasionally colonized by Giardia. All mammalian isolates are currently classified as Giardia lamblia, although some nomenclature systems use the name G. duodenalis or G. intestinalis. Recent DNA sequence technology suggests that one or two distinct Giardia genotypes can be isolated exclusively from dogs, and a distinct genetic group can be isolated from cats. It is not clear whether differences in pathogenicity exist between these genotypes. Giardia species have a worldwide distribution. Because Giardia is maintained in nature primarily by fecal-oral transmission, more cases are associated with crowded and unsanitary conditions. A recent study showed a prevalence in the dog of 7.2%.

Pathophysiology of Giardia

Giardia spp. are found on the surface of enterocytes, where the trophozoites attach to the brush border of the epithelium. Specific histologic changes have not been reported, but persistence of infection may promote apoptosis and inhibition of re-epithelialization.

Clinical examination

Although infected animals may remain asymptomatic, clinical signs such as acute or chronic diarrhea, weight loss, or even acute or chronic vomiting may develop. Although Giardia cysts and trophozoites have been found in the feces of dogs with both small bowel and large bowel diarrhea, Giardia infection is primarily a problem of the small intestine.

Diagnosis of Giardia

Giardia infections can be diagnosed by demonstrating motile trophozoites on fresh fecal smears or cysts by zinc sulfate sedimentation. Commercial enzyme-linked immunosorbent assay (ELISA) kits have also been used to detect Giardia antigen in fresh fecal samples. Enzyme-linked immunosorbent assay assays may be slightly more sensitive and specific than a single zinc sulfate concentrating technique in diagnosing Giardia infections in dogs. A direct immunofluorescent antibody test has been used in the diagnosis of Giardia infections in humans, but it has not yet been validated in the dog. Duodenal aspirates during gastrointestinal endoscopy appear to be ineffective in diagnosing Giardia infection.

Treatment of Giardia

Metronidazole, ipronidazole, fenbendazole, albendazole, and a praziquantel, pyrantel pamoate, febantel combination have all been used in the treatment of Giardia infections with varying levels of success. A Giardia vaccine has been shown to be effective in prevention and therapy in dogs, but efficacy has not yet been established in cats.

Prognosis of Giardia

The prognosis for long-term health and recovery is generally very favorable.

Isospora cants, Isospora ohioensis, Isospora felis, Isospora neorivoha

The Isospora species are the most common coccidial parasites of dogs (Isospora canis and Isospora ohioensis) and cats (Isospora felis and Isospora neorivoha). The coccidia are primarily parasites of the small intestine, but Isospora ohioensis may induce cecal and colonic pathology in puppies and young dogs. Sulfadimethoxine (50 mg / kg orally, once a day for 10 days) or sulfatrimethoprim (15 to 30 mg / kg orally, once a day for 5 days) may be used where clinical signs warrant treatment.

Tritrichomonas foetus

Tritrichomonas foetus: Cause

Tritrichomonas foetus is a flagellated protozoan parasite that is an important venereal pathogen in cattle. T. foetus has also been identified as an intestinal pathogen in domestic cats from which intraluminal infection of the colon leads to chronic large bowel diarrhea. Infected cats are usually young and frequently reside in densely populated housing such as catteries or animal shelters. Cats often have a history of infection with Giardia spp.; these infections are subsequently identified as trichomoniasis after failure to eradicate the organisms with standard antiprotozoal treatment (e. g., metronidazole or fenbendazole).


After experimental inoculation in cats, Tritrichomonas foetus organisms have been shown to colonize the ileum, cecum, and colon, reside in close contact with the epithelium, and are associated with transient diarrhea that is exacerbated by coexisting cryptosporidiosis.

Clinical examination

Infected animals have clinical signs that are consistent with chronic colitis-type diarrhea.

Diagnosis of Tritrichomonas foetus

Diagnosis of trichomonosis in cats is made by direct observation of trichomonads in samples of freshly voided feces that are suspended in physiologic saline (0.9% NaCl) solution and examined microscopically at x200 to x400 magnification. Tritrichomonas foetus can also be grown from feces via incubation at 37° C. in Diamond’s medium. The sensitivity of direct examination of a fecal smear for diagnosis of T. foetus in naturally infected cats is unknown but is suspected to be poor. A commercially available culture system that is sensitive and specific for culture of Tritrichomonas foetus will improve the diagnostic outcome. These kits are most useful when inoculated with less than or equal to 0.1 g of fresh feces at 25° C. More recently, a single-nested tube polymerase chain reaction technique has been developed that is ideally suited for diagnostic testing of feline lecal samples that are found negative by direct microscopy and by definitive identification of microscopically observable or cultivated organisms.

Treatment of Tritrichomonas foetus

At this time the origin of the infection in most cats is unknown, and no effective antimicrobial treatment exists for Tritrichomonas foetus infection. Metronidazole and fenbendazole may improve clinical signs but generally do not resolve infection. Nitazoxanide eliminates shedding of Tritrichomonas foetus and Gryptosporidium oocysts, but diarrhea and oocyst shedding recur with discontinuation of treatment. A series of cats that were treated with paromomycin for Tritrichomonas foetus infection subsequently developed kidney failure. Consequently, paromomycin should probably not be used in cats.

Prognosis of Tritrichomonas foetus

The prognosis for eradication of the organism is not encouraging at this time.